Affinage

PIM3

Serine/threonine-protein kinase pim-3 · UniProt Q86V86

Length
326 aa
Mass
35.9 kDa
Annotated
2026-04-28
81 papers in source corpus 35 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIM3 is a constitutively active serine/threonine kinase of the CaMK group that functions as a pro-survival and pro-tumorigenic signaling node, integrating transcriptional inputs from ETS-family factors, c-Myc, STAT3, and YY1 with post-translational stabilization by TCTP to phosphorylate substrates that govern apoptosis, cell migration, stemness, and chromatin state (PMID:16818649, PMID:12748291, PMID:19154409, PMID:21646687, PMID:24165482, PMID:36150380). Its best-characterized kinase activity is phosphorylation of the pro-apoptotic protein BAD at Ser112, which inactivates BAD and suppresses apoptosis across pancreatic, colon, and liver cancers; additional direct substrates include KSHV LANA (Ser205/206), MLF2 (Ser65), CXCR4 (Ser339), and MAPK1 (T185/Y187), linking PIM3 to viral reactivation, metastasis via the IRE1α/XBP1-S axis, chemokine receptor signaling, and MAPK pathway activation (PMID:16818649, PMID:19266083, PMID:41090348, PMID:36315303, PMID:38128397). PIM3 also maintains endothelial barrier integrity by sustaining junctional VE-cadherin and catenin complexes, and in embryonic stem cells it suppresses the 2-cell-like totipotent state through an AMPK–HDAC4/5–H3K9ac chromatin axis (PMID:39627185, PMID:36150380). Its expression is negatively regulated by mTORC1-driven miR-33a, which directly targets the PIM3 3′-UTR (PMID:29167471, PMID:25971209).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Establishing that PIM3 is an oncogenic kinase: its identification as a transcriptional target of EWS/ETS fusions, combined with the finding that kinase-dead PIM3 suppresses transformation, demonstrated that PIM3 kinase activity is required for EWS/FLI1-driven tumorigenesis.

    Evidence Microarray, kinase-dead mutant (K69M) overexpression, NIH 3T3 soft agar and nude mouse tumorigenesis assays

    PMID:12748291

    Open questions at the time
    • Direct phosphorylation substrates unidentified at this stage
    • Endogenous relevance beyond Ewing sarcoma unknown
  2. 2005 High

    Defining PIM3 as an anti-apoptotic, pro-proliferative kinase: siRNA-mediated knockdown in hepatoma cells showed PIM3 is required for cell survival, establishing its role in epithelial cancer beyond Ewing sarcoma.

    Evidence RNA interference in human hepatoma cell lines with proliferation and apoptosis assays

    PMID:15540201

    Open questions at the time
    • Molecular substrates mediating anti-apoptotic effect unknown
    • In vivo relevance not yet tested
  3. 2006 High

    Identifying BAD Ser112 as the key pro-survival substrate: PIM3 directly phosphorylates BAD at Ser112 (not Ser136) to inactivate its pro-apoptotic function, providing the first defined substrate mechanism for PIM3-mediated survival signaling, replicated across pancreatic, colon, and liver cancer.

    Evidence shRNA knockdown, phospho-BAD Western blot, apoptosis assays in pancreatic and colon cancer cells; IHC co-localization in clinical tissues

    PMID:16818649 PMID:17270021

    Open questions at the time
    • Whether BAD is the sole survival substrate unclear
    • Structural basis of PIM3-BAD interaction unresolved
  4. 2007 High

    Positioning PIM3 downstream of STAT3 in stem cell biology: PIM3 was shown to be a STAT3-regulated gene in ES cells that promotes self-renewal and prevents apoptosis, expanding its role beyond cancer to developmental biology.

    Evidence Chimeric gp130 receptor, STAT3-ER inducible system, shRNA knockdown, clonal self-renewal assay in mouse ESCs

    PMID:17717068

    Open questions at the time
    • Direct STAT3 binding to PIM3 promoter not shown by ChIP in this study
    • Substrates mediating ES cell self-renewal undefined
  5. 2008 High

    Defining transcriptional regulation of PIM3: Ets-1 was shown to directly bind the PIM3 promoter and drive constitutive expression, with c-Myc later shown to bind E-boxes within the Pim3 gene, establishing PIM3 as a convergence point of multiple oncogenic transcription factors.

    Evidence ChIP, luciferase reporter with promoter deletions, epistasis rescue (Ets-1 KD rescued by PIM3 cDNA); ChIP for c-Myc on Pim3 E-boxes in Burkitt lymphoma

    PMID:19154409 PMID:21646687

    Open questions at the time
    • Relative contribution of Ets-1 vs c-Myc vs STAT3 in different contexts not resolved
    • Chromatin-level regulation of PIM3 promoter accessibility unknown
  6. 2009 High

    Expanding PIM3 substrates to viral latency and revealing non-cancer functions: PIM3 phosphorylates KSHV LANA at Ser205/206 to relieve transcriptional repression and enable lytic reactivation; separately, PIM3 localizes to lamellipodia in endothelial cells and is required for EC migration and tube formation.

    Evidence Co-IP, phosphorylation mapping, lytic gene transcription analysis for LANA; immunofluorescence co-localization with FAK, siRNA, Matrigel assay for ECs

    PMID:19229879 PMID:19266083

    Open questions at the time
    • Whether PIM3 kinase activity is directly required for lamellipodia localization unclear
    • In vivo relevance of PIM3 in angiogenesis not yet demonstrated
  7. 2010 High

    Demonstrating PIM3 as a tumor promoter in vivo and identifying a metabolic substrate: liver-specific PIM3 transgenic mice develop accelerated HCC only with carcinogen co-treatment, establishing PIM3 as a promoter not initiator; separately, PIM3 negatively regulates insulin secretion via SOCS6-mediated ERK1/2 inhibition in β-cells.

    Evidence Liver-selective transgenic mouse with DEN; Pim3-/- knockout mice with glucose tolerance testing, Co-IP of PIM3-SOCS6

    PMID:20101231 PMID:21099329

    Open questions at the time
    • Direct phosphorylation of SOCS6 by PIM3 not demonstrated
    • Mechanism by which PIM3 accelerates cell cycle in hepatocytes beyond BAD unclear
  8. 2013 High

    Revealing post-translational control of PIM3 stability: TCTP/TPT1 physically interacts with PIM3's C-terminus and protects it from ubiquitin-proteasome degradation, establishing that PIM3 protein levels are controlled at the post-translational level in addition to transcriptional regulation.

    Evidence Yeast two-hybrid, Co-IP, domain mapping, proteasome inhibitor rescue, RNAi of TCTP

    PMID:24165482

    Open questions at the time
    • E3 ligase responsible for PIM3 ubiquitination not identified
    • Whether TCTP-PIM3 interaction is regulated by signaling unknown
  9. 2015 Medium

    Identifying miR-33a as a negative regulator targeting PIM3 mRNA: miR-33a directly targets the PIM3 3′-UTR, and mTORC1 drives miR-33 expression via SREBP1/2, creating a feedback loop where mTORC1 activity suppresses PIM3.

    Evidence Dual luciferase reporter for 3′-UTR targeting; rapamycin treatment, TSC-null cells, in vivo mouse liver feeding model

    PMID:25971209 PMID:29167471

    Open questions at the time
    • Functional importance of mTORC1-miR-33-PIM3 axis in specific disease contexts not established
    • Whether other miRNAs regulate PIM3 not explored systematically
  10. 2017 Medium

    Linking PIM3 to cancer stemness and STAT3-mediated EMT: PIM3 activates STAT3 phosphorylation to maintain pancreatic cancer stemness and promotes melanoma metastasis through STAT3-driven Slug/Snail/ZEB1 expression.

    Evidence siRNA with STAT3 rescue in pancreatic CSCs; shRNA with in vivo lung metastasis model in melanoma

    PMID:28775772 PMID:29370558

    Open questions at the time
    • Whether PIM3 directly phosphorylates STAT3 or acts through an intermediary kinase not resolved
    • Mechanism of PIM3 selectivity for stem-like subpopulations undefined
  11. 2020 Medium

    Identifying RhoA and CXCR4 as PIM3-regulated effectors of cell migration: phosphoproteomics revealed PIM3 activates RhoA GTPase signaling for cytoskeletal rearrangement in liver cancer, and PIM3 phosphorylates CXCR4 at Ser339 to promote AML cell chemotaxis.

    Evidence Quantitative phosphoproteomics with RhoA activity assay; Co-IP of PIM3-pCXCR4 with migration assay

    PMID:31994402 PMID:32764981

    Open questions at the time
    • Direct PIM3-RhoA phosphorylation event not identified
    • CXCR4 Ser339 phosphorylation by PIM3 shown by single Co-IP without in vitro kinase assay confirmation
  12. 2022 High

    Revealing a chromatin-regulatory role in totipotency suppression: PIM3 knockout in ESCs activates the MuERVL-marked 2-cell-like state through increased AMPK phosphorylation, nuclear export of HDAC4/5, and consequent H3K9 hyperacetylation on endogenous retroviral elements.

    Evidence Pim3 KO ESCs, AMPK phosphorylation analysis, HDAC4/5 localization, H3K9ac/me ChIP at MuERVL loci

    PMID:36150380

    Open questions at the time
    • Whether PIM3 directly phosphorylates AMPK or suppresses its activation indirectly unknown
    • Relevance of this axis in preimplantation embryos in vivo not tested
  13. 2022 High

    Validating CXCR4 as an in vivo metastatic effector downstream of PIM3: CRISPR knockout and overexpression combined with pharmacologic CXCR4 blockade (AMD3100) in hepatoblastoma demonstrated PIM3-CXCR4 epistasis in metastatic colonization.

    Evidence CRISPR/Cas9 KO and OE, tail-vein metastasis model, AMD3100 rescue, flow cytometry for surface CXCR4

    PMID:33864024 PMID:36315303

    Open questions at the time
    • Whether PIM3-CXCR4 axis operates in non-hepatoblastoma metastasis unknown
    • Contribution of CXCR4 phosphorylation vs. surface trafficking not disentangled
  14. 2024 High

    Uncovering a tumor-suppressive context: endothelial PIM3 maintains VE-cadherin-based adherens junctions to preserve vascular barrier integrity, and PIM inhibition paradoxically increases metastatic colonization by disrupting the endothelial barrier.

    Evidence scRNA-seq of lung ECs, spontaneous metastasis models, PIM inhibitor treatment, junction protein analysis

    PMID:39627185

    Open questions at the time
    • Direct PIM3 substrate maintaining junctional stability not identified
    • Whether this barrier-protective role counteracts tumor-cell-intrinsic PIM3 oncogenic effects in clinical settings unknown
  15. 2025 High

    Identifying MLF2 Ser65 as a metastasis-promoting substrate and MAPK1 as a direct PIM3 substrate: PIM3 phosphorylates MLF2 at Ser65, stabilizing it via USP21 and activating the IRE1α/XBP1-S-MMP9 metastatic axis; separately, PIM3 phosphorylates MAPK1 at T185/Y187 to drive ESCC proliferation.

    Evidence CRISPR activation screen, Co-IP, phosphosite mapping, ubiquitination assay for MLF2; pull-down, CETSA, kinase assay for MAPK1 in PDX model

    PMID:38128397 PMID:41090348

    Open questions at the time
    • Whether MLF2 phosphorylation is PIM3-specific or shared with PIM1/PIM2 not tested
    • Structural basis for PIM3 dual Ser/Thr and Tyr kinase activity on MAPK1 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of PIM3 substrate selectivity, whether PIM3 directly phosphorylates STAT3 or AMPK, the identity of the E3 ligase that ubiquitinates PIM3, and how tumor-cell-intrinsic oncogenic activity is reconciled with endothelial barrier-protective functions in therapeutic targeting.
  • No crystal structure of PIM3 (only PIM1 co-crystal reported)
  • E3 ubiquitin ligase for PIM3 not identified
  • Context-dependent tumor-promoting vs. barrier-protective functions not reconciled mechanistically

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-4839726 Chromatin organization 1
Partners
BADCXCR4MAPK1MLF2SOCS6STAT3TCTP

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 PIM3 phosphorylates the pro-apoptotic protein BAD at Ser112 (but not Ser136) to inactivate it and prevent apoptosis in human pancreatic cancer cells; knockdown of PIM3 reduced BAD phosphorylation at Ser112 and Bcl-XL expression, promoting apoptosis. shRNA knockdown, Western blot for phospho-BAD (Ser112/Ser136), sub-G1 cell cycle analysis, phosphatidylserine externalization assay Cancer research High 16818649
2007 PIM3 phosphorylates BAD at Ser112 in human colon cancer cells, and PIM3 co-localizes with phospho-Ser112-BAD in clinical colon cancer tissues, inactivating BAD to prevent apoptosis. shRNA knockdown, Western blot, immunohistochemistry co-localization Cancer science High 17270021
2005 PIM3 promotes hepatoma cell proliferation and prevents apoptosis; siRNA-mediated ablation of PIM3 attenuates proliferation and enhances apoptosis in human hepatoma cell lines. RNA interference, cell proliferation assay, apoptosis assay International journal of cancer High 15540201
2003 PIM3 is a direct transcriptional target of EWS/ETS fusion oncoproteins; forced expression of PIM3 promotes anchorage-independent growth, and a kinase-deficient PIM3 mutant attenuates EWS/FLI1-mediated tumorigenesis, demonstrating that PIM3 kinase activity is required for its oncogenic function downstream of EWS/ETS. Microarray expression analysis, NIH 3T3 tumorigenesis assay, kinase-dead mutant overexpression, immunodeficient mouse model Molecular and cellular biology High 12748291
2009 PIM3 phosphorylates the KSHV latency-associated nuclear antigen LANA at serine residues 205 and 206, counteracting LANA-mediated repression of KSHV lytic gene transcription and enabling viral reactivation. Co-immunoprecipitation, phosphorylation mapping, overexpression of Pim-1/Pim-3, analysis of KSHV lytic gene transcription PLoS pathogens High 19266083
2007 PIM3 expression is regulated by the LIF/gp130/STAT3 signaling pathway in mouse embryonic stem cells; PIM3 supports ES cell self-renewal and prevents apoptosis downstream of STAT3. Chimeric receptor system, hormone-dependent STAT3-ER construct, overexpression and shRNA knockdown, clonal self-renewal assay Stem cells High 17717068
2008 The transcription factor Ets-1 directly binds the 5'-flanking region of the human PIM3 gene (between -249 and -183 bp, with an Ets-1 binding site at -216 to -211 bp) and drives constitutive PIM3 expression in pancreatic cancer cells; Ets-1 knockdown reduces BAD phosphorylation at Ser112 and induces apoptosis, which is rescued by PIM3 cDNA overexpression. Luciferase reporter assay with deletion mutants, chromatin immunoprecipitation (ChIP), dominant-negative Ets-1, siRNA, Western blot, rescue experiment Cancer science High 19154409
2013 Translationally controlled tumor protein (TCTP/TPT1) interacts with PIM3 through PIM3's C-terminal region and TCTP's N-terminal region, and stabilizes PIM3 protein via protection from ubiquitin-proteasome degradation; TCTP knockdown reduces PIM3 protein but not mRNA. Yeast 2-hybrid screen, Co-IP, mapping studies, RNAi, proteasome inhibitor assays, in vitro and in vivo tumor assays Molecular cancer research High 24165482
2011 PIM3 is a direct c-Myc transcriptional target; c-Myc binds conserved E-boxes within the Pim3 gene, and Myc-transgenic mouse lymphomas as well as Burkitt lymphoma cell lines exhibit elevated Pim-3 levels. ChIP (c-Myc binding to Pim3 E-boxes), gene expression analysis in Myc-transgenic lymphomas and cell lines, pan-PIM inhibitor cell death assay Oncotarget High 21646687
2009 PIM3 is expressed in endothelial cells, localizes to lamellipodia and co-localizes with focal adhesion kinase (FAK); PIM3 is dispersed from lamellipodia by cytochalasin D (actin polymerization inhibitor), and siRNA knockdown of PIM3 impairs EC spreading, migration, proliferation, and tube formation on Matrigel. Immunofluorescence/co-localization, cytochalasin D treatment, siRNA knockdown, Matrigel tube formation assay Journal of cellular physiology Medium 19229879
2009 PIM3 up-regulation via p38 MAPK signaling protects cardiomyocytes against anoxia/reoxygenation injury; inhibition of p38 MAPK by SB203580 abolishes both PIM3 up-regulation and anoxic preconditioning-mediated cardioprotection. Pim-3 expression vector transfection, p38 MAPK inhibitor SB203580, cardiomyocyte A/R model International journal of biochemistry & cell biology Medium 19505587
2010 PIM3 overexpression in the liver accelerates hepatocellular carcinoma development induced by diethylnitrosamine but does not cause HCC alone, indicating PIM3 acts as a tumor promoter rather than initiator; transgenic hepatocytes show accelerated cell cycle progression. Liver-selective PIM3 transgenic mice, diethylnitrosamine treatment, histological analysis, PCNA/CD31 staining Oncogene High 20101231
2010 PIM3 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cells by inhibiting ERK1/2 activation through SOCS6; PIM3 physically interacts with SOCS6 and Pim3-/- islets show reduced SOCS6 and increased ERK1/2 phosphorylation, augmenting second-phase insulin secretion. Microarray on glucose-stimulated MIN6 cells, Pim3-/- knockout mice, Co-immunoprecipitation (PIM3-SOCS6 interaction), SOCS6 overexpression inhibition of ERK1/2, glucose tolerance test Islets High 21099329
2014 PIM3 promotes pancreatic cancer angiogenesis in vivo through upregulation of VEGF; kinase-dead PIM3 (K69M) abolished enhanced Bad-Ser112 phosphorylation, angiogenesis, and tumor neovascularization, confirming kinase-activity dependence. Stable cell lines with WT vs K69M kinase-dead PIM3, nude mouse orthotopic xenograft, MRI tumor measurement, VEGF ELISA, CD31 staining The Journal of surgical research / Oncology reports High 23845873 24789328
2017 mTORC1 suppresses PIM3 expression via SREBP1/2-driven miR-33, which targets PIM3 mRNA; rapamycin (mTORC1 inhibitor) increases PIM3 transcript and protein, and this is dependent on reduced miR-33 expression. Rapamycin treatment, TSC knockout cells, miR-33 expression analysis, mTORC1 activation models in vivo (mouse liver feeding) Scientific reports Medium 29167471 29170467
2015 miR-33a directly targets the PIM3 3'-UTR to suppress PIM3 expression, leading to downregulation of the AKT/GSK-3β/β-catenin pathway and increased sensitivity to gemcitabine in pancreatic cancer cells. Luciferase reporter assay (miR-33a targeting PIM3 3'-UTR), miR-33a overexpression, Western blot for AKT/GSK-3β/β-catenin Oncotarget Medium 25971209
2018 PIM3 promotes melanoma cell migration and invasion by phosphorylating/activating STAT3 (Tyr705), which induces expression of EMT factors Slug, Snail, and ZEB1. shRNA knockdown, tumor-bearing mouse model for lung metastasis, Western blot for pSTAT3 Cancer biology & therapy Medium 29370558
2020 PIM3 promotes cell migration in liver cancer by activating RhoA GTPase and regulating cytoskeletal rearrangements; quantitative phosphoproteomics revealed that PIM3 overexpression elevates phosphorylation of multiple Rho GTPase modulators targeting RhoA. Quantitative proteomics and phosphoproteomics, RhoA activity assay, cytoskeletal imaging, migration assay Journal of proteome research Medium 31994402
2022 PIM3 suppresses the MuERVL-marked 2-cell-like state in embryonic stem cells via an AMPK-HDAC4/5 axis: loss of PIM3 leads to increased AMPK phosphorylation, which phosphorylates HDAC4/5, causing their nuclear export, reducing H3K9ac deacetylation and increasing H3K9ac/decreasing H3K9me1/2 on MuERVL, activating 2-cell genes. Pim3 KO ESCs, AMPK phosphorylation assay, HDAC4/5 nuclear localization, H3K9ac/H3K9me ChIP, PIM3 inhibitor treatment Stem cell reports High 36150380
2020 PIM3 overexpression promotes AML cell migration via phosphorylation of CXCR4 at Ser339; PIM3 physically interacts with phosphorylated CXCR4, and PIM3-overexpressing AML cells show increased cell surface CXCR4 and chemotaxis. Co-immunoprecipitation (PIM3-pCXCR4), Western blot (pCXCR4-Ser339), cell migration assay, immunofluorescence OncoTargets and therapy Medium 32764981
2022 PIM3 promotes hepatoblastoma metastasis by upregulating cell surface expression and phosphorylation of CXCR4; CXCR4 blockade with AMD3100 decreased the metastatic phenotype of PIM3-overexpressing cells, establishing CXCR4 as a downstream effector of PIM3-driven metastasis. CRISPR/Cas9 PIM3 knockout, PIM3 overexpression, tail-vein injection metastasis model, AMD3100 CXCR4 inhibition, flow cytometry for cell surface CXCR4 Clinical & experimental metastasis High 36315303
2021 CRISPR/Cas9-mediated PIM3 knockout in hepatoblastoma cells decreases proliferation, viability, motility, and tumor growth in xenograft model, decreases tumorsphere formation and stemness markers including CD133, and reintroduction of PIM3 rescues the malignant phenotype. CRISPR/Cas9 dual-gRNA PIM3 knockout, xenograft, tumorsphere assay, RNA-seq, flow cytometry for CD133, PIM3 rescue Cancer gene therapy High 33864024
2025 PIM3 phosphorylates MLF2 at Ser65, enhancing MLF2 stabilization through USP21 interaction and preventing STUB1-mediated ubiquitination and proteasomal degradation; MLF2 stabilization activates the IRE1α/XBP1-S-MMP9 axis to promote osteosarcoma lung metastasis. In vivo CRISPR activation screen, Co-IP, phosphorylation site mapping, ubiquitination assay, STUB1 interaction assay, USP21 interaction assay The Journal of clinical investigation High 41090348
2025 PIM3 physically interacts with and activates the Akt signaling pathway in nucleus pulposus cells, regulating downstream mTOR and FoxO1 to maintain cell viability and suppress senescence; these effects require PIM3 kinase activity. Co-immunoprecipitation (PIM3-Akt), kinase-dead PIM3 experiments, Western blot for p-Akt/mTOR/FoxO1, AAV-mediated PIM3 overexpression in rat IDD model Translational research Medium 41478528
2017 In HTLV-1-infected T cells, Tax induces PIM3 expression through NF-κB; PIM3 knockdown inhibits growth of HTLV-1-infected T cells, and a Pim-1/3 inhibitor induces G2/M arrest and apoptosis by downregulating cyclin A, cyclin B1, XIAP, and Mcl-1 through NF-κB pathway inhibition. siRNA knockdown, EMSA (NF-κB DNA binding), RT-PCR, cell cycle analysis, pharmacologic Pim-1/3 inhibitor European journal of haematology Medium 28833639
2016 PIM3 promotes radioresistance in pancreatic cancer cells by attenuating G2/M cell cycle arrest and DNA damage response; PIM3 silencing increases γH2AX phosphorylation (DNA DSB marker) and decreases ATM kinase activation and its downstream targets. Stable PIM3 overexpression and siRNA knockdown, radiation treatment, γH2AX assay, ATM/downstream target Western blot, in vivo xenograft with radiation Biochemical and biophysical research communications Medium 27016481
2019 Aldosterone stimulates PIM3 expression in the aldosterone-sensitive distal nephron in vitro, ex vivo, and in vivo; Pim3-/- mice show upregulated RAAS with high circulating aldosterone and plasma renin activity, and compensatory upregulation of PIM1 and PIM2 in kidney. Germline Pim3-/- knockout mice, mCCDcl1 cell aldosterone treatment, mouse kidney slice assays, RAAS measurement Physiological reports Medium 31397090
2024 Endothelial PIM3 protects the vascular barrier against metastatic colonization by maintaining junctional VE-cadherin (cadherin-5) and catenins α, β, and δ; PIM inhibition increases vascular leakage and metastatic colonization in lung. scRNA-seq of lung ECs, spontaneous metastasis models, PIM inhibitor treatment, junction protein Western blot/immunofluorescence, lung metastasis quantification Nature communications High 39627185
2019 PIM3 promotes cholesterol-driven colorectal cancer cell proliferation and survival by phosphorylating p27, p21, and BAD; cholesterol suppresses miR-33a, leading to PIM3 upregulation, and miR-33a directly targets PIM3 as confirmed by dual luciferase reporter assay. Dual luciferase reporter assay, miR-33a mimics/inhibitor, Western blot for p27/p21/pBAD, CCK8, flow cytometry Biochemical and biophysical research communications Medium 30827510
2017 PIM3 regulates pancreatic cancer cell stemness via activating STAT3 signaling; PIM3 silencing decreases phosphorylation and transcriptional activity of STAT3, and STAT3 reactivation rescues the stem cell-like phenotype lost upon PIM3 knockdown. Pim-3 siRNA, CD24/ESA sorting for cancer stem cell subpopulations, STAT3 phosphorylation assay, STAT3 rescue experiment, tumorsphere and tumorigenicity assays Journal of Cancer Medium 28775772
2025 The natural compound CSH-4044 (isolated from fermented wheat germ extract) inhibits PIM3 kinase activity in an ATP-competitive manner (co-crystal structure with PIM1 determined), and suppresses PIM3-driven BAD phosphorylation at Ser112 in pancreatic cancer cells. X-ray crystallography (PIM1 co-crystal structure), kinase profiling, phospho-BAD Western blot in pancreatic cancer cells bioRxivpreprint Medium
2023 PIM3 phosphorylates MAPK1 at T185 and Y187 in esophageal squamous cell carcinoma cells to promote proliferation and tumor development; corynoline directly binds PIM3, inhibits its kinase activity, and suppresses ESCC growth. Pull-down assay, cellular thermal shift assay, kinase assay, phosphorylation site identification, patient-derived xenograft tumor model Phytomedicine Medium 38128397
2025 ETS1 transcription factor transcriptionally upregulates PIM3 in myocardial ischemia-reperfusion injury; hyperglycemia similarly drives nuclear translocation of YY1, which binds the PIM3 promoter and enhances PIM3 transcriptional activity, promoting cardiac hypertrophy. ChIP assay (YY1 binding to Pim3 promoter), luciferase reporter assay, ETS1/YY1 knockdown, mouse MIRI and diabetic models Experimental cell research / Iranian journal of basic medical sciences Medium 39850120 40189183

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines. Cancer research 156 16818649
2007 Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis. Cancer science 109 17270021
2005 Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines. International journal of cancer 87 15540201
2012 Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases. Bioorganic & medicinal chemistry letters 83 22727640
2011 Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer science 74 21518143
2003 PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins. Molecular and cellular biology 68 12748291
2007 Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression. Journal of cancer research and clinical oncology 66 17876606
2015 MicroRNA-33a-mediated downregulation of Pim-3 kinase expression renders human pancreatic cancer cells sensitivity to gemcitabine. Oncotarget 63 25971209
2009 KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. PLoS pathogens 60 19266083
2007 Self-renewal of murine embryonic stem cells is supported by the serine/threonine kinases Pim-1 and Pim-3. Stem cells (Dayton, Ohio) 58 17717068
2010 Accelerated hepatocellular carcinoma development in mice expressing the Pim-3 transgene selectively in the liver. Oncogene 56 20101231
2019 Cholesterol regulates cell proliferation and apoptosis of colorectal cancer by modulating miR-33a-PIM3 pathway. Biochemical and biophysical research communications 45 30827510
2013 A novel regulatory mechanism of Pim-3 kinase stability and its involvement in pancreatic cancer progression. Molecular cancer research : MCR 42 24165482
2011 The direct Myc target Pim3 cooperates with other Pim kinases in supporting viability of Myc-induced B-cell lymphomas. Oncotarget 41 21646687
2016 MiR-377 inhibits the proliferation of pancreatic cancer by targeting Pim-3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 27638830
2011 Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases. Bioorganic & medicinal chemistry letters 40 21945284
2008 Essential contribution of Ets-1 to constitutive Pim-3 expression in human pancreatic cancer cells. Cancer science 36 19154409
2014 Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression. World journal of gastroenterology 34 25071334
2009 Pim-3 is expressed in endothelial cells and promotes vascular tube formation. Journal of cellular physiology 31 19229879
2013 Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine. Cancer biology & therapy 29 23760491
2009 Pim-3 protects against cardiomyocyte apoptosis in anoxia/reoxygenation injury via p38-mediated signal pathway. The international journal of biochemistry & cell biology 27 19505587
2018 Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation. Cancer biology & therapy 26 29370558
2017 Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells. Oncotarget 26 29069816
2016 Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells. Biochemical and biophysical research communications 21 27016481
2015 MicroRNA‑506 participates in pancreatic cancer pathogenesis by targeting PIM3. Molecular medicine reports 20 26238203
2014 Pim-3 promotes human pancreatic cancer growth by regulating tumor vasculogenesis. Oncology reports 20 24789328
2019 Bufothionine exerts anti-cancer activities in gastric cancer through Pim3. Life sciences 19 31260686
2019 AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK. International journal of molecular sciences 18 30654529
2015 Aberrant expression of pim-3 promotes proliferation and migration of ovarian cancer cells. Asian Pacific journal of cancer prevention : APJCP 18 25921139
2014 Differential expression of Pim-3, c-Myc, and p-p27 proteins in adenocarcinomas of the gastric cardia and distal stomach. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 24488669
2009 Pim-3 protects against hepatic failure in D-galactosamine (D-GalN)-sensitized rats. European journal of clinical investigation 17 20039932
2010 Pim3 negatively regulates glucose-stimulated insulin secretion. Islets 16 21099329
2021 CRISPR/Cas9-mediated knockout of PIM3 suppresses tumorigenesis and cancer cell stemness in human hepatoblastoma cells. Cancer gene therapy 15 33864024
2013 Pim-3 promotes the growth of human pancreatic cancer in the orthotopic nude mouse model through vascular endothelium growth factor. The Journal of surgical research 15 23845873
2005 Association of the PIM3 allele of the alpha-1-antitrypsin gene with chronic obstructive pulmonary disease. Clinical biochemistry 15 15820782
2017 Pim-3 as a potential predictor of chemoradiotherapy resistance in locally advanced rectal cancer patients. Scientific reports 14 29167471
2020 PIM3 Promotes the Proliferation and Migration of Acute Myeloid Leukemia Cells. OncoTargets and therapy 13 32764981
2015 Knockdown of Pim-3 suppresses the tumorigenicity of glioblastoma by regulating cell cycle and apoptosis. Cellular and molecular biology (Noisy-le-Grand, France) 13 25817345
2024 PIM3 Kinase: A Promising Novel Target in Solid Cancers. Cancers 11 38339286
2020 Proto-Oncogene Serine/Threonine Kinase PIM3 Promotes Cell Migration via Modulating Rho GTPase Signaling. Journal of proteome research 11 31994402
2019 The presence of PIM3 increases hepatoblastoma tumorigenesis and tumor initiating cell phenotype and is associated with decreased patient survival. Journal of pediatric surgery 11 30898394
2009 [Effect of ginsenoside Rg3 on Pim-3 and Bad proteins in human pancreatic cancer cell line PANC-1]. Ai zheng = Aizheng = Chinese journal of cancer 11 19624871
2022 PIM3-AMPK-HDAC4/5 axis restricts MuERVL-marked 2-cell-like state in embryonic stem cells. Stem cell reports 10 36150380
2018 PIM3 Functions as Oncogenic Factor and Promotes the Tumor Growth and Metastasis in Colorectal Cancer. Anatomical record (Hoboken, N.J. : 2007) 10 30417983
2017 Pim-3 Regulates Stemness of Pancreatic Cancer Cells via Activating STAT3 Signaling Pathway. Journal of Cancer 10 28775772
2015 Design and synthesis of an in vivo-efficacious PIM3 kinase inhibitor as a candidate anti-pancreatic cancer agent. Bioorganic & medicinal chemistry letters 10 26547690
2023 Predictive Value of PRISM-4, PIM-3, CRP, Albumin, CRP/Albumin Ratio and Lactate in Critically Ill Children. Children (Basel, Switzerland) 7 38002822
2023 Corynoline inhibits esophageal squamous cell carcinoma growth via targeting Pim-3. Phytomedicine : international journal of phytotherapy and phytopharmacology 7 38128397
2020 High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms. Endocrine pathology 7 32504181
2019 Effect of Pim-3 Downregulation on Proliferation and Apoptosis in Lung Adenocarcinoma A549 Cells. Annals of clinical and laboratory science 7 31882428
2017 mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci. Scientific reports 7 29170467
2015 Overexpression of pim-3 and protective role in lipopolysaccharide-stimulated hepatic stellate cells. World journal of gastroenterology 7 26269675
2015 Binding site identification and role of permanent water molecule of PIM-3 kinase: A molecular dynamics study. Journal of molecular graphics & modelling 7 26529487
2021 LncRNA RGMB-AS1 facilitates pancreatic cancer cell proliferation and migration but inhibits cell apoptosis via miR-574-3p/PIM3 axis. American journal of physiology. Gastrointestinal and liver physiology 6 34468207
2019 Pim-3 alleviates lipopolysaccharide-stimulated AR42J pancreatic acinar cell injury via improving the inflammatory microenvironment. Experimental and therapeutic medicine 6 31777546
2017 Up-regulation of Pim-3 in Chronic Obstructive Pulmonary Disease (COPD) patients and its potential therapeutic role in COPD rat modeling. Pathology, research and practice 6 28214201
2017 Expression and significance of Pim-3 kinase in adult T-cell leukemia. European journal of haematology 6 28833639
2014 Serine threonine kinase Pim-3 regulates STAT3 pathway to inhibit proliferation of human liver cancers. International journal of clinical and experimental medicine 6 24600488
2024 Endothelial Pim3 kinase protects the vascular barrier during lung metastasis. Nature communications 5 39627185
2023 PIM3 regulates myocardial ischemia/reperfusion injury via ferroptosis. Genes & genomics 5 38148455
2022 PIM3 kinase promotes tumor metastasis in hepatoblastoma by upregulating cell surface expression of chemokine receptor cxcr4. Clinical & experimental metastasis 5 36315303
2019 Downregulation of microRNA-124 prevents the development of acute liver failure through the upregulation of PIM-3. Experimental physiology 5 31628693
2025 Metabolic reprogramming through PIM3 inhibition reverses hypoxia-induced CAR-T cell dysfunction in solid tumors. Journal of translational medicine 4 41199316
2022 Long non-coding RNA long intergenic non-protein coding RNA 1232 promotes cell proliferation, migration and invasion in bladder cancer via modulating miR-370-5p/PIM3 axis. Journal of tissue engineering and regenerative medicine 4 35338769
2022 Long non-coding RNA (FALEC) promotes malignant behaviors of gastric cancer cells by regulating miR-203b/PIM3 axis. Annals of translational medicine 4 35722357
2022 Multi-stage analysis of FOXM1, PYROXD1, hTERT, PPARA, PIM3, BMI1 and MCTP1 expression patterns in colorectal cancer. Gastroenterology and hepatology from bed to bench 4 35845311
2019 The serine-threonine kinase PIM3 is an aldosterone-regulated protein in the distal nephron. Physiological reports 4 31397090
2025 ETS1 modulates ferroptosis to affect the process of myocardial ischemia-reperfusion injury via PIM3. Experimental cell research 3 40189183
2024 Low miR-936-mediated upregulation of Pim-3 drives sorafenib resistance in liver cancer through ferroptosis inhibition by activating the ANKRD18A/Src/NRF2 pathway. Frontiers in oncology 3 39507762
2007 [Protective role of Pim-3 gene in intestinal mucosa damaged by burn or lipopolysaccharide]. Zhonghua yi xue za zhi 3 18261321
2025 Pim3 up-regulation by YY1 contributes to diabetes-induced cardiac hypertrophy and heart failure. Iranian journal of basic medical sciences 1 39850120
2024 Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3. Bioorganic & medicinal chemistry letters 1 38199328
2023 LncRNA SNHG1 Accelerates Cell Proliferation, Migration, and Invasion of Hepatoblastoma Through Mediating miR-6838-5p/PIM3/RhoA Axis. Biochemical genetics 1 37248373
2023 Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3. bioRxiv : the preprint server for biology 1 38106118
2018 [Effects of endotoxin/lipopolysaccharide on early apoptosis of human neutrophil through PIM3]. Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns 1 30481923
2016 [Expression and Significance of Pim-3 Gene in Acute Myeloid Leukemia]. Zhongguo shi yan xue ye xue za zhi 1 27150984
2012 [Inhibitive mechanisms of Pim-3 affecting fulminant hepatic apoptosis]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 1 23207234
1996 Low frequency of PIM3 gene in patients with monoclonal gammopathies. Human heredity 1 8666412
2025 PIM3-mediated phosphorylation stabilizes myeloid leukemia factor 2 to promote metastasis in osteosarcoma. The Journal of clinical investigation 0 41090348
2025 PIM3 enhances nucleus pulposus cell function and extracellular matrix integrity via kinase-dependent activation of the Akt/mTOR signaling axis in intervertebral disc degeneration. Translational research : the journal of laboratory and clinical medicine 0 41478528
2007 [Construction of a recombinant Pim3-expressing plasmid and expression and activity thereof: experiment with rats]. Zhonghua yi xue za zhi 0 18067836