| 1993 |
The EMS1 gene product (human cortactin, 80/85 kDa) is homologous (85% identity) to a chicken v-src substrate. In normal epithelial cells, the protein localizes mainly to the cytoplasm with minor presence in leading lamellae; in carcinoma cells overexpressing EMS1, it accumulates at podosome-like adherens junctions associated with cell-substratum contact sites, but not intercellular adherens junctions. |
Amino acid sequence comparison, immunocytochemistry |
Molecular and cellular biology |
Medium |
8474448
|
| 1998 |
The EMS1/cortactin protein contains: (i) a filamentous actin-binding tandem repeat domain, (ii) a proline-rich SH3-binding region, and (iii) a SH3 domain. Both human p80 and p85 isoforms are encoded by the EMS1 cDNA. Expression is restricted to non-lymphoid tumor cell lines. |
Gene transfer experiments, western blot, sequence analysis |
Cell adhesion and communication |
Medium |
9823470
|
| 1998 |
Stable overexpression of EMS1/cortactin in NIH3T3 fibroblasts increases cell motility and invasiveness in modified Boyden chamber assays without altering proliferation or anchorage independence, indicating cortactin promotes cell migration and invasion. |
Stable transfection, modified Boyden chamber motility/invasion assay, proliferation assay |
Oncogene |
Medium |
9681820
|
| 1999 |
EGF treatment or cell detachment induces an 80–85 kDa mobility shift of EMS1 (cortactin) correlated with increased serine/threonine phosphorylation. This shift is blocked by the MEK inhibitor PD98059 and is induced by constitutively active MEK, establishing MEK as a necessary and sufficient intermediate in EMS1 phosphorylation. The helical-proline-rich region is required for this phosphorylation. ERKs are candidate kinases for this region in vitro, but other MEK-regulated enzymes also participate. |
Pharmacological inhibition (PD98059), constitutively active MEK expression, in vitro kinase assay, deletion mutagenesis, tryptic phosphopeptide mapping |
Cancer research |
High |
10537323
|
| 1996 |
EMS1 protein is tyrosine phosphorylated in breast cancer cell lines; degree of tyrosine phosphorylation correlates with src-family kinase activity (c-fyn and c-yes expression). Gene amplification is the predominant mechanism of EMS1 overexpression in breast cancer cell lines. |
Western blot, tyrosine phosphorylation analysis, src kinase activity assay |
International journal of cancer |
Medium |
8945620
|
| 2006 |
siRNA-mediated silencing of CTTN in esophageal squamous cell carcinoma cells reduces cell migration, invasiveness, and anoikis resistance. The protective role of CTTN in anoikis resistance correlates with activation of the PI3K/Akt pathway. In vivo, CTTN knockdown decreased tumor growth and lung metastasis. |
siRNA knockdown, cell migration assay, anoikis assay, PI3K/Akt signaling analysis, in vivo xenograft |
Cancer research |
High |
17178864
|
| 2009 |
Calreticulin (CRT) regulates CTTN expression via STAT3: CRT knockdown reduces p-STAT3, and chromatin immunoprecipitation shows direct binding of p-STAT3 to STAT3-binding sequences in the CTTN promoter. CRT-enhanced anoikis resistance and motility operate through a CRT–STAT3–CTTN–PI3K–Akt pathway; CTTN restoration in CRT-depleted cells rescues motility and anoikis resistance. |
siRNA knockdown, ChIP assay, JAK inhibitor (AG490), Western blot, cell migration/invasion/anoikis assays, CTTN rescue experiment |
Oncogene |
High |
19684620
|
| 2019 |
RNF128 (an E3 ubiquitin ligase) ubiquitinates and promotes degradation of CTTN (cortactin), activating Wnt/β-catenin signaling and CD44/c-Myc transcription. RNF128 downregulation leads to CTTN accumulation, inducing EMT and stemness in melanoma. |
Co-IP, ubiquitination assay, siRNA interference, functional EMT/stemness assays |
Journal of hematology & oncology |
Medium |
30832692
|
| 2020 |
UCHL1 interacts with CTTN and promotes K48-linked ubiquitination of CTTN, leading to its proteasomal degradation. CTTN rescue in UCHL1-overexpressing NPC cells restores migration and invasion, placing CTTN as a functional downstream target of UCHL1. |
Co-IP, ubiquitination assay (K48-linkage specific), in vitro/in vivo migration and invasion assays, CTTN rescue experiment |
Cells |
Medium |
32120844
|
| 2022 |
The CTTN coding SNP Ser484Asn (rs56162978) reduces Tyr486 cortactin phosphorylation, inhibits binding of cortactin to nmMLCK, delays endothelial cell barrier recovery after thrombin-induced permeability, and attenuates lamellipodia dynamics. In Cttn+/- heterozygous mice, increased lung vascular permeability was rescued by WT CTTN transgene but not by S484N transgene. |
Transgene expression in human lung ECs, phosphorylation assay, Co-IP (cortactin–nmMLCK binding), biophysical barrier assay, liposome-mediated transgene delivery in vivo in ARDS mouse model |
Translational research |
High |
35181549
|
| 2022 |
CBLC (an E3 ubiquitin ligase) interacts with CTTN in the cytoplasm and promotes CTTN degradation through the ubiquitin-proteasome pathway without affecting CTTN mRNA levels. CBLC-mediated inhibition of breast cancer cell proliferation, migration, and invasion is partially reversed by CTTN overexpression. |
Co-IP, immunofluorescence co-localization, ubiquitin-proteasome pathway assay, rescue experiment with CTTN overexpression |
Journal of receptor and signal transduction research |
Medium |
36043996
|
| 2008 |
Cortactin (CTTN) and N-WASP, two regulators of actin network assembly, are concentrated at tubulobulbar complexes in the rat testis seminiferous epithelium alongside clathrin, supporting that these podosome-like structures involve cortactin-dependent actin assembly and clathrin-mediated endocytosis. |
Immunofluorescence microscopy, immunoelectron microscopy on rat testis |
Biology of reproduction |
Low |
18799755
|
| 2011 |
siRNA silencing of cortactin (CTTN) in colon cancer cells reduces transferrin uptake (endocytosis). Intact cortactin protein and sufficient expression level are required for optimal clathrin-coated vesicle-mediated endocytosis in cancer cells. |
siRNA knockdown, domain-deletion mutant transfection, transferrin uptake assay, immunohistochemistry |
Zhonghua yi xue za zhi |
Medium |
21418910
|
| 2019 |
CTTN overexpression downregulates DKK-1, a Wnt antagonist, thereby activating Wnt/β-catenin signaling. A β-catenin/TCF inhibitor reverses CTTN-induced cancer stem cell-like properties in HER2+ breast cancer cells in vitro. |
RNA-seq, Western blot, tumorsphere formation, ALDEFLUOR assay, in vivo xenograft, β-catenin/TCF inhibitor treatment |
Cancers |
Medium |
36831511
|
| 2024 |
Matrix stiffness promotes cell migration, invasion, and invadopodia formation in nasopharyngeal carcinoma through upregulation of wild-type CTTN (WT-CTTN). The splicing factor PTBP2 (activated by high stiffness) controls the production of WT-CTTN over splice variants (SV1-CTTN, SV2-CTTN), establishing a PTBP2–WT-CTTN axis in mechanosensing. |
siRNA knockdown, overexpression studies, alternative splicing analysis, migration/invasion/invadopodia assays in varying stiffness conditions |
Cancer science |
Medium |
38273817
|
| 2019 |
HBx (hepatitis B virus X protein) physically interacts with CTTN in HCC cells (validated by Co-IP and confocal microscopy). The HBx–CTTN interaction upregulates CREB1 and its downstream targets (cyclin D1, MMP-9), promoting cell proliferation and migration. |
Proteomics, Co-IP, confocal microscopy, cell proliferation/migration assays, cell cycle analysis |
Cell death & disease |
Medium |
31138777
|
| 2024 |
YWHAG (14-3-3γ) interacts with CTTN and mediates CRC cell proliferation, migration, and invasion by activating Wnt/β-catenin signaling downstream of CTTN. |
RNA-seq, Co-IP (YWHAG–CTTN interaction), functional cell assays, Wnt signaling readouts |
Medical oncology |
Low |
38538804
|
| 2025 |
RBMS1 promotes alternative splicing of CTTN to generate a CTTN-Δe11 isoform in cardiomyocytes. This splicing switch activates the PI3K/AKT signaling pathway, causing cytoskeleton and sarcomere damage leading to cardiac hypertrophy. |
RNA splicing analysis, PI3K/AKT pathway assay, cardiac hypertrophy mouse model, pharmacological inhibition of RBMS1 (nortriptyline) |
EMBO molecular medicine |
Medium |
41214391
|
| 2025 |
Cortactin localizes to Rab7-positive late endosomes and is required for late endosomal tethering and homeostasis. Cortactin depletion in circulating tumor cells causes accumulation of aberrantly enlarged Rab7+ late endosomal aggregates, accumulation and activation of mTOR within these structures, p53 phosphorylation (Ser15, Ser33), G0/G1 cell cycle arrest, and cellular senescence (characterized by SASP, β-galactosidase activity, Ki-67/Lamin B1 depletion, elevated mitochondrial ROS). A positive p53–mtROS feedback loop maintains stable senescence. |
Live imaging and fractionation (Rab7/mTOR localization), CTTN depletion, p53 phosphorylation assay, cell cycle analysis, senescence markers (β-gal, SASP, Ki-67, Lamin B1, mtROS), CDX mouse models |
bioRxivpreprint |
Medium |
bio_10.1101_2025.03.26.645381
|
| 2025 |
Knockdown of CTTN in HNSCC cells reduces FAK expression levels and impairs cytoskeletal formation, thereby reducing anoikis resistance. CTTN silencing also suppresses growth in patient-derived organoids (PDOs). |
siRNA knockdown, PI staining (apoptosis), immunofluorescence, Western blot (FAK), PDO culture assays |
Scientific reports |
Medium |
41168318
|
| 2025 |
LAD1 (ladinin-1) binds LINC01305 and together they co-regulate phosphorylation of CTTN and N-WASP, mediating cytoskeletal reorganization and EMT via activation of the PI3K/AKT signaling pathway in ESCC cells. |
Co-IP (LAD1–LINC01305), phosphorylation assays (CTTN, N-WASP), PI3K/AKT pathway analysis, EMT marker analysis |
Molecular carcinogenesis |
Low |
39835575
|
| 2024 |
LPS, TNF-α, and high-magnitude cyclic stretch (18% CS) significantly increase CTTN promoter activity; these responses require NF-κB response elements in the promoter. The promoter SNP rs34612166 (−212T/C) markedly enhances LPS- and 18%CS-induced CTTN promoter activation. HIF pathway activators and NRF2 also modulate CTTN promoter activity. Demethylation (5'-Aza) increases CTTN promoter activity ~2.9-fold, indicating epigenetic regulation. |
Luciferase reporter assay with full-length CTTN promoter, site-directed mutagenesis (NF-κB sites and SNP), pharmacological modulators (HIF, NRF2 inhibitors/activators, 5'-Aza), cyclic stretch, immunohistochemistry in LPS-exposed mouse lungs |
Bioscience reports |
Medium |
39162263
|