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Showing CERS2 — LASS2 is a alias.

CERS2

Ceramide synthase 2 · UniProt Q96G23

Length
380 aa
Mass
44.9 kDa
Annotated
2026-06-09
61 papers in source corpus 29 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CERS2 (LASS2) is an endoplasmic reticulum-resident ceramide synthase that selectively acylates sphingoid bases with very-long-chain acyl-CoAs (C22–C24), making it the principal enzyme generating very-long-chain (VLC) ceramides in vivo (PMID:19801672). Its catalytic output is set post-translationally: casein kinase 2 phosphorylates cytoplasmic C-terminal residues to raise its Vmax, and dephosphorylation collapses activity toward C22:0/C24:0-CoA substrates (PMID:26887952). Through this VLC-ceramide supply, CERS2 governs tissue-specific physiology — it is expressed in oligodendrocytes and Schwann cells during active myelination and is required for myelin maintenance, as its loss causes myelin and cerebellar degeneration (PMID:19801672, PMID:17901973), and it is required for β-cell insulin secretion and glucose homeostasis, with a partial loss-of-function allele (rs267738/E115A) impairing both (PMID:33705551, PMID:39792658). Disrupting CERS2 distorts the ceramide pool (falling VLC, rising long-chain species), triggering growth arrest, autophagy, and PERK/IRE1 unfolded-protein-response activation (PMID:19728861). Beyond its enzymatic role, CERS2 acts as a tumor suppressor through a distinct protein-interaction module: it binds the V-ATPase C subunit ATP6V0C via its homeodomain to inhibit proton-pump activity, raising extracellular pH and suppressing pH-dependent MMP-2/9 activation, migration, and invasion (PMID:22991218, PMID:25213553); this anti-invasive function is itself gated by phosphorylation at C-terminal serines (PMID:41399074, PMID:30996356). CERS2 additionally engages MDM2/MDMX to stabilize and activate p53 (PMID:37963859), physically associates with the calcium channel IP3R1 to drive ER–mitochondria Ca²⁺ flux and apoptosis upon pharmacologic activation (PMID:42012500), and binds TFRC to modulate iron homeostasis and ferroptosis (PMID:38419028).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 Medium

    Tested whether human LASS2/CERS2 is functionally equivalent to its yeast ortholog Lag1p, probing the role of its homeodomain.

    Evidence Yeast complementation shuffling/tetrad tests with full-length and ΔHOX LASS2 from LAG1 or ADH1 promoters

    PMID:16765836

    Open questions at the time
    • Negative complementation does not define the biochemical activity LASS2 actually carries
    • Does not establish the homeodomain's true binding function
  2. 2007 High

    Established where and when CERS2 acts, localizing its expression to myelinating glia during active myelination.

    Evidence In situ hybridization, Northern blot, RT-PCR across mouse brain development and sciatic nerve

    PMID:17901973

    Open questions at the time
    • Expression mapping alone does not prove a causal myelin requirement
  3. 2009 High

    Defined CERS2 as the principal enzyme for very-long-chain ceramide synthesis and showed its loss disrupts myelin maintenance, connecting an enzymatic activity to a tissue phenotype.

    Evidence Gene-trap knockout mouse with ceramide synthase activity assays, lipidomics, myelin biochemistry, and electron microscopy

    PMID:19801672

    Open questions at the time
    • Does not resolve how altered ceramide chain length mechanically destabilizes myelin
    • Whole-body knockout cannot separate glial-intrinsic from systemic effects
  4. 2009 Medium

    Showed that CERS2 loss not only depletes VLC ceramides but reciprocally raises long-chain ceramides and triggers stress programs, linking ceramide-pool balance to autophagy and the UPR.

    Evidence siRNA knockdown with mass spectrometry sphingolipid profiling and UPR/autophagy assays

    PMID:19728861

    Open questions at the time
    • The ceramide-synthase-independent rise in C14/C16 ceramide is unexplained
    • Single-lab cell-based system
  5. 2010 Medium

    Opened a non-catalytic, pH-based tumor-suppressor axis by linking CERS2 to V-ATPase and mitochondrial apoptosis.

    Evidence Overexpression in V-ATPase-related pH and apoptosis assays in hepatocellular carcinoma cells

    PMID:20571735

    Open questions at the time
    • Did not yet demonstrate direct CERS2–V-ATPase binding
    • Mechanistic link between pH and apoptosis correlative
  6. 2013 High

    Identified the molecular basis of CERS2's pH control by demonstrating a direct homeodomain-mediated interaction with the V-ATPase C subunit ATP6V0C.

    Evidence Reciprocal co-IP, immuno-electron microscopy, domain-deletion mutants, BCECF pH assay

    PMID:22991218

    Open questions at the time
    • Structural details of the homeodomain–ATP6V0C contact not resolved
    • Relationship between catalytic and V-ATPase-regulatory functions unclear
  7. 2012 Medium

    Generalized the V-ATPase-dependent invasion-suppression mechanism across breast and prostate cancer models, tying it to MMP activation and chemosensitivity.

    Evidence Gain/loss-of-function in cancer cell lines with pH, MMP zymography, invasion, drug-uptake and xenograft assays

    PMID:22573553 PMID:22580606

    Open questions at the time
    • Single-lab models
    • Contribution of CERS2 enzymatic activity to these effects not isolated
  8. 2015 Medium

    Solidified the V-ATPase/pH/MMP invasion axis bidirectionally, showing CERS2 dose tunes extracellular acidification and MMP-2/9 activity.

    Evidence Bidirectional overexpression/knockdown with V-ATPase, pH, zymography, transwell assays

    PMID:25213553

    Open questions at the time
    • Single-lab
    • Does not connect to phosphorylation control identified later
  9. 2016 High

    Revealed CK2 phosphorylation of CERS2's cytoplasmic C-terminus as the principal post-translational switch controlling its catalytic rate, and identified ASGR1 as an upstream regulator of its V-ATPase function.

    Evidence Phosphoproteomics, CK2 inhibitor CX-4945, site-directed mutagenesis, brain dephosphorylation activity assays; separately co-IP and knockdown epistasis for ASGR1

    PMID:26887952 PMID:27241665

    Open questions at the time
    • How phosphorylation alters Vmax structurally unknown
    • Whether the same phosphosites govern catalytic and V-ATPase roles not resolved
  10. 2018 Medium

    Extended CERS2 tumor-suppressor signaling to mitochondrial dynamics, ROS/MAPK signaling, and hepatic metabolism through tissue-specific deletion.

    Evidence Hepatocyte-specific knockout and gain-of-function with ERK/Drp1 inhibitors, mitochondrial staining, ROS and MAPK readouts

    PMID:29581781 PMID:29626628

    Open questions at the time
    • Relationship between V-ATPase, ROS and ERK/Drp1 effects not fully ordered
    • Single-lab models
  11. 2021 High

    Mapped specific phosphoserines (S248) controlling CERS2-driven β-catenin degradation and tied CERS2 activity to oncogene-induced senescence and β-cell glucose homeostasis.

    Evidence Phospho-deficient mutants and co-IP with STK38/SCYL2/ATP6V0C; CerS2/SK1 siRNA epistasis with senescence markers; CRISPR knock-in and knockout mice with glucose/islet assays

    PMID:33414460 PMID:33705551 PMID:33852174

    Open questions at the time
    • How a single enzyme coordinates V-ATPase, β-catenin and metabolic roles is unresolved
    • Phosphosite numbering varies across studies
  12. 2023 Medium

    Defined a p53-dependent tumor-suppressor mechanism whereby CERS2 binds MDM2/MDMX to block p53 degradation and promote its nuclear activation.

    Evidence Co-IP with MDM2/MDMX, p53 PTM western blots, immunofluorescence localization in hepatoma cells

    PMID:37963859

    Open questions at the time
    • Direct vs. indirect MDM2/MDMX binding not structurally defined
    • Single-lab overexpression-based
  13. 2024 Medium

    Broadened CERS2's interactome to PP2A/β-catenin chemoresistance control and to TFRC-mediated iron homeostasis and ferroptosis as anti-metastatic mechanisms.

    Evidence Co-IP/LC-MS, ChIP, PP2A activity and PDX assays; reciprocal co-IP, PLA and ferroptosis epistasis (Fer-1/erastin) across multiple cancer types

    PMID:38191448 PMID:38419028

    Open questions at the time
    • Whether these interactions occur in the same cells/conditions as the V-ATPase axis is unknown
    • Single-lab studies
  14. 2025 High

    Demonstrated that direct pharmacologic activation of CERS2 drives VLC-ceramide accumulation, ER stress, and an IP3R1-dependent ER–mitochondria Ca²⁺/apoptosis axis, providing a druggable mechanistic loop.

    Evidence Small-molecule agonist DH20931 with CerS2-KO resistance, enzymatic assay, CerS2–IP3R1 co-IP, ER stress blots, ER–mito proximity and Ca²⁺ measurements, xenografts

    PMID:39792658 PMID:42012500

    Open questions at the time
    • Structural basis of agonist binding not defined
    • Whether the IP3R1 interaction depends on catalytic activity unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the single CERS2 protein partitions between its VLC-ceramide catalytic activity and its many non-catalytic protein interactions (V-ATPase, MDM2/MDMX, PP2A, TFRC, IP3R1), and whether these interactions are mutually exclusive, context-specific, or coordinately regulated by phosphorylation.
  • No structure of CERS2 or its interaction interfaces
  • No study isolating catalytic-dead vs. interaction-dead alleles across the diverse phenotypes
  • Most interaction findings come from single labs without reciprocal cross-validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ASGR1ATP6V0CIP3R1MDM2MDMXNDUFS2STK38TFRC

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 CERS2 (CerS2/LASS2) encodes a ceramide synthase with substrate specificity toward very-long-chain fatty acid residues (C22–C24); knockout mice lack ceramide synthase activity toward C24:1 in brain and liver, and show strongly reduced ceramide species with acyl chains ≥C22 in liver, kidney, and brain, establishing CERS2 as the principal enzyme responsible for very-long-chain ceramide synthesis in vivo. Gene-trap knockout mouse (lacZ reporter), ceramide synthase activity assays, lipidomic analysis of brain/liver/kidney The Journal of biological chemistry High 19801672
2009 CERS2 deficiency in mice causes progressive loss of myelin stainability (~50% loss of compacted myelin, ~80% loss of myelin basic protein), vesiculation and multifocal detachment of inner myelin lamellae in ~20% of peripheral nervous system axons, and cerebellar degeneration with microcysts, establishing CERS2 activity as required for myelin maintenance. Gene-trap knockout mouse, myelin biochemistry (MBP western blot), electron microscopy of peripheral nerve The Journal of biological chemistry High 19801672
2007 CerS2 expression in mouse brain is specifically localized to white matter tracts (oligodendrocytes) and is transiently increased during the period of active myelination; CerS2 is also the predominant ceramide synthase in Schwann cells of sciatic nerves, establishing its cell-type-specific role in myelin sphingolipid synthesis. In situ hybridization, Northern blot, real-time RT-PCR in mouse brain during postnatal development Histochemistry and cell biology High 17901973
2009 CerS2 knockdown by siRNA causes broad disruption of ceramide homeostasis: VLC ceramides (C24, C24:1) decrease, while LC ceramides (C14, C16) increase via a ceramide-synthase-independent mechanism; this results in growth arrest without apoptosis, induction of autophagy, and activation of PERK and IRE1 arms of the unfolded protein response. siRNA knockdown, mass spectrometry-based sphingolipid analysis, autophagy and UPR assays The Biochemical journal Medium 19728861
2016 CERS2 (and CERS3–6) are phosphorylated at cytoplasmic C-terminal residues, predominantly by casein kinase 2 (CK2); phosphorylation of CERS2 is especially important for its catalytic activity, primarily increasing its Vmax. Treatment with CK2-specific inhibitor CX-4945 lowered phosphorylation and reduced CERS2 activity; dephosphorylation of brain ceramide synthases severely reduced activity toward C22:0/C24:0-CoA substrates. Phosphoproteomic analysis, CK2 inhibitor (CX-4945) treatment, in vitro ceramide synthase activity assays, site-directed mutagenesis of phosphorylation sites, mouse brain dephosphorylation experiments The Journal of biological chemistry High 26887952
2013 LASS2/CERS2 protein interacts directly with the C subunit of vacuolar H+-ATPase (V-ATPase, ATP6V0C), and this interaction is mediated specifically through the homeodomain of LASS2; loss of the homeodomain abolishes the ability to regulate V-ATPase activity and intracellular pH, while variants retaining the homeodomain reduce V-ATPase activity. Co-immunoprecipitation, immunofluorescence, immuno-electron microscopy, domain-deletion mutant transfection, BCECF/AM pH fluorescence assay Journal of cellular biochemistry High 22991218
2012 LASS2/CERS2 overexpression in MCF-7/ADR breast cancer cells increases extracellular and lysosomal pH by inhibiting V-ATPase activity, resulting in increased intracellular retention of doxorubicin and increased chemosensitivity; LASS2 knockdown in MCF-7 cells decreased chemosensitivity. LASS2 overexpression/siRNA knockdown, pH measurement, drug uptake assays, apoptosis assays, nude mouse xenograft Oncogene Medium 22580606
2015 CERS2 overexpression in highly invasive MDA-MB-231 breast cancer cells inhibits migration and invasion by reducing V-ATPase activity, increasing extracellular pH, and decreasing pH-dependent activation of secreted MMP-2 and MMP-9; conversely, CERS2 knockdown in MCF7 cells increases V-ATPase activity, decreases extracellular pH, and increases MMP-2/9 activity and invasiveness. Overexpression/siRNA knockdown, V-ATPase activity assay, extracellular pH measurement, gelatin zymography for MMP-2/9, transwell invasion assay Journal of cellular biochemistry Medium 25213553
2012 Silencing of LASS2/TMSG1 in the prostate cancer cell line PC-3M-2B4 increases V-ATPase activity, raises extracellular hydrogen ion concentration, activates secreted MMP-2, and enhances migration and invasion in vitro, confirming that LASS2 suppresses cancer invasion through regulation of V-ATPase activity. siRNA knockdown, V-ATPase activity assay, pH-sensitive fluorescence probes, gelatin zymography, Matrigel invasion assay Journal of cellular biochemistry Medium 22573553
2010 LASS2 overexpression in hepatocellular carcinoma HCCLM3 cells (which lack endogenous LASS2) increases intracellular H+ and decreases extracellular H+ via interaction with V-ATPase, and induces apoptosis through a mitochondrial pathway involving cytochrome c release from mitochondria and caspase-3 activation. Transient transfection, BCECF/BCECF-AM pH fluorescence probes, Annexin V/PI flow cytometry, cytochrome c western blot Acta physiologica Sinica Medium 20571735
2021 Phosphorylated LASS2 promotes β-catenin degradation through physical interaction with STK38, SCYL2, and ATP6V0C via the ubiquitin-proteasome pathway; phosphorylation at serine residue 248 of LASS2 is essential for this function. Dephosphorylation of LASS2 at S248 significantly enhances prostate cancer cell growth and metastasis in vivo. Co-immunoprecipitation, phosphorylation-deficient mutant (S248A), ubiquitin-proteasome pathway assays, in vivo xenograft Journal of cellular biochemistry Medium 33852174
2025 Dephosphorylation of LASS2 at serine residue 348 (identified by mass spectrometry) significantly enhances prostate cancer cell growth, migration and invasion through increasing V-ATPase activity, extracellular hydrogen ion concentration, and secretion of active MMP-2; the phosphatase inhibitor calyculin A reduces growth and invasion of aggressive prostate cancer cells. Mass spectrometry phosphosite mapping, phosphorylation-deficient mutants (S341A, S348A, S349A), V-ATPase activity assay, pH measurement, gelatin zymography, Matrigel invasion, pharmacological calyculin A treatment Beijing da xue xue bao. Yi xue ban Medium 41399074
2019 The S248A phosphorylation-deficient mutant of LASS2 promotes proliferation, migration and invasion of prostate cancer cells through increasing ATP6V0C (V-ATPase C subunit) expression, establishing that phosphorylation at aa248–250 is a key functional site for LASS2-mediated invasion suppression. Phosphorylation-deficient mutant construction, co-immunofluorescence colocalization with ATP6V0C, western blot, MTT, migration and invasion assays Beijing da xue xue bao. Yi xue ban Medium 30996356
2016 ASGR1 (asialoglycoprotein receptor) directly interacts with LASS2/CERS2; ASGR1 overexpression decreases V-ATPase activity in hepatoma cells, and this effect is reversed by LASS2 knockdown, placing LASS2 downstream of ASGR1 in regulating V-ATPase-mediated tumor cell invasion. Co-immunoprecipitation (direct protein-protein interaction), LASS2 siRNA knockdown, V-ATPase activity assay, Matrigel invasion assay Cancer letters Medium 27241665
2018 LASS2 overexpression induces mitochondrial fusion (elongation), reduces p-Drp1 and Fis1 expression, decreases mitochondrial membrane potential, and inhibits bladder cancer invasion and chemoresistance; these effects are mediated upstream through inhibition of ERK phosphorylation, which normally activates Drp1. ERK inhibitor PD98059 phenocopies LASS2 overexpression on Drp1 status. LASS2 plasmid transfection and siRNA knockdown, MitoTracker and JC-1 staining, western blot (p-ERK, p-Drp1, Fis1), Drp1 inhibitor Mdivi-1, ERK inhibitor PD98059, Matrigel invasion and apoptosis assays Journal of Cancer Medium 29581781
2018 LASS2 overexpression in hepatocytes decreases V-ATPase activity and increases ROS, activating p38 MAPK and ERK1/2 signaling; hepatocyte-specific LASS2 knockout mice are resistant to high-fat diet-induced hepatic steatosis and insulin resistance, associated with elevated V-ATPase activity and reduced ROS and downstream MAPK signaling. Hepatocyte-specific CERS2 knockout (Cre-LoxP), high-fat diet feeding, V-ATPase activity assay, ROS measurement, western blot (p38 MAPK, ERK1/2), LASS2 overexpression in AML12 cells Free radical biology & medicine Medium 29626628
2013 Hepatocyte-specific Lass2/CERS2 knockout mice exposed to diethylnitrosamine (DEN) show enhanced liver tumorigenesis and elevated expression of PAI-1, TGF-β1 and Smad4 (not Smad7), suggesting LASS2 suppresses liver carcinogenesis in part by restraining the TGF-β1–Smad4–PAI-1 axis. Hepatocyte-specific knockout mouse, DEN carcinogenesis model, PCNA/EdU proliferation assay, TUNEL apoptosis assay, qPCR, western blot Oncology reports Medium 24337404
2017 Liver-specific LASS2/CERS2 deletion delays liver regeneration after partial hepatectomy, with reduced PCNA, Ki67, cyclin A, CDK2, p-Rb, and decreased CDK4/cyclin D1 complex formation; delayed regeneration is partially compensated by late Akt phosphorylation activation. Liver-specific CERS2 knockout (Cre-LoxP), partial hepatectomy, co-immunoprecipitation (CDK4/cyclin D1), immunohistochemistry, western blot Biochemical and biophysical research communications Medium 28958935
2021 CerS2 downregulation by siRNA blocks the increase in VLC ceramides (C24, C24:1, C26:1) induced by SK1 knockdown and phenocopies fumonisin B1 (a pan-CerS inhibitor) in blocking p21 upregulation during oncogene-induced senescence in MCF10A cells expressing oncogenic K-Ras, demonstrating that CerS2-generated VLC ceramides are required for VLC ceramide accumulation and oncogene-induced senescence downstream of SK1 inhibition. siRNA knockdown of CerS2 and SK1, sphingolipid mass spectrometry, SA-β-gal assay, p21 western blot, fumonisin B1 treatment, cell-cycle analysis Cell death & disease Medium 33414460
2024 LASS2/CERS2 directly interacts with transferrin receptor (TFRC) as identified by co-IP coupled LC-MS; LASS2 overexpression regulates iron homeostasis and ferroptosis status in thyroid, breast, and liver cancer cells, inhibiting tumor migration, invasion and EMT, and this anti-metastatic effect is reversed by ferroptosis inhibitor Fer-1. Co-IP LC-MS proteomics, protein-protein docking, co-IP western blot, immunofluorescence, proximity ligation assay, ferroptosis assays (Fer-1/erastin treatment), invasion and EMT assays Cancer cell international Medium 38419028
2023 LASS2 interacts with MDM2 and MDMX, causing dual inhibition that disrupts p53 degradation; LASS2 overexpression induces p53 phosphorylation at Ser15 and acetylation at Lys373, promoting p53 translocation from cytoplasm to nucleus in hepatoma cells (HepG2, HCCLM3, HuCCT1), establishing a p53-dependent tumor suppressor mechanism for LASS2 in liver cancer. Co-immunoprecipitation, gene set enrichment analysis, immunofluorescence, western blot (p-p53, acetyl-p53), gain-of-function overexpression Cell death discovery Medium 37963859
2024 LASS2 inhibits PP2A activity and dissociates PP2A from β-catenin, preventing dephosphorylation of β-catenin and leading to accumulation of cytosolic phospho-β-catenin, which decreases transcription of ABCC2 and CD44 in bladder cancer stem cells, thereby sensitizing them to cisplatin. Co-immunoprecipitation, LC-MS proteomic identification of PP2A interaction, luciferase reporter assay, chromatin immunoprecipitation, PP2A activity assay, cell-derived and patient-derived xenograft models, LASS2 gain/loss of function BMC medicine Medium 38191448
2021 Nrf2 transcriptionally activates LASS2/CERS2 expression by binding to antioxidant response elements (AREs) in the LASS2 promoter (three AREs identified), as demonstrated by luciferase reporter assay; Nrf2/LASS2 overexpression results in progestin resistance in endometrial cancer cells. Luciferase reporter assay (ARE-containing LASS2 promoter constructs), Nrf2 siRNA knockdown, western blot, RT-PCR, proliferation/apoptosis assays American journal of translational research Medium 33841656
2021 Whole-body Cers2 knockout and rs267738 (E115A) CRISPR knock-in mice both exhibit glucose intolerance and impaired insulin secretion in vivo; islets from these models show reduced β-cell function with decreased insulin secretion ex vivo, and knock-in mice have reduced liver CERS2 activity, establishing this SNP as a partial loss-of-function allele that impairs glucose homeostasis. CRISPR knock-in mouse (rs267738), whole-body CERS2 knockout mouse, glucose tolerance tests, insulin secretion assays, ex vivo islet function, liver ceramide synthase activity assay, targeted lipidomics The Journal of clinical endocrinology and metabolism High 33705551
2025 Both whole-body Cers2 knockout and rs267738 knock-in mice show glucose intolerance and impaired insulin secretion; islets from these models show reduced β-cell function (decreased ex vivo insulin secretion), confirming that CERS2 activity is required for normal β-cell function and glucose homeostasis. Cers2 knockout mouse, rs267738 knock-in mouse, glucose tolerance tests, in vivo and ex vivo insulin secretion, lipidomics, GWAS integration Science advances High 39792658
2020 LASS2 interacts with NDUFS2 (a subunit of mitochondrial complex I/OXPHOS), as identified by co-IP combined with LC-MS; LASS2 overexpression increases mitochondrial ROS (mtROS) and promotes AMPK phosphorylation, leading to inhibition of lipogenesis (decreased SREBP1, FAS) and promotion of lipolysis (increased ATGL, HSL), thereby reducing hepatocyte steatosis. Co-immunoprecipitation + LC-MS (NDUFS2 identification), LASS2 overexpression/knockdown in FFA-treated Hepa1-6 cells and mouse primary hepatocytes, mtROS measurement, AMPK/ACC phosphorylation western blot Biochemical and biophysical research communications Low 32279995
2014 Renal sulfatide distribution is regionally determined by sphingoid base composition (C18-sphingosine in cortex/medulla, C18-phytosphingosine restricted to cortical structures, C20-sphingosine exclusively in papillae); CerS2 deletion causes bulk loss of C23/C24-acyl sulfatides and complete depletion of phytosphingosine-containing cortical sulfatides without compensation, revealing that CERS2 is required for synthesis of this specific sulfatide subclass. MALDI imaging mass spectrometry, LC-MS/MS of regional renal lipids, CerS2 knockout mouse, regional mRNA analysis of biosynthetic enzymes Journal of lipid research Medium 25267995
2017 Knockdown of CerS2 in CHO-IgG cells alters cellular ceramide composition and, in combination with knockdown of Tbc1D20, recapitulates the increased antibody secretory productivity induced by mitosRNA-1978, suggesting CERS2 function at the ER influences vesicular trafficking in the secretory pathway. siRNA/shRNA knockdown in CHO cells, ceramide composition analysis, IgG productivity measurement, fed-batch production assay Metabolic engineering Low 28088541
2025 A novel small-molecule agonist DH20931 directly activates CerS2 (genetic evidence: CerS2 KO cells are resistant to DH20931), causing VLCC accumulation that induces ER stress via ATF4/CHOP/PUMA; CerS2 physically interacts with the ER calcium channel IP3R1 (co-IP), and DH20931 promotes this interaction, enhancing ER–mitochondria proximity and Ca²⁺ flux into mitochondria to trigger apoptosis. CerS2 knockout genetic validation, in vitro ceramide synthase activity assay, co-immunoprecipitation (CerS2–IP3R1), ER stress pathway western blots, ER–mitochondria proximity assay, mitochondrial Ca²⁺ measurement, orthotopic and PDX xenograft models Molecular cancer therapeutics High 42012500
2005 LASS2/CERS2 cannot functionally complement yeast Lag1p even when expressed from the strong ADH1 promoter or its natural LAG1 promoter; neither full-length LASS2 nor the LASS2ΔHOX fragment (lacking the homeodomain/HOX domain) rescues the slow growth defect of lag1Δlac1Δ double mutants, establishing functional non-equivalence between LASS2 and its yeast ortholog Lag1p. Yeast complementation (shuffling test, tetrad analysis) with LASS2 and LASS2ΔHOX expressed from LAG1 or ADH1 promoters Microbiological research Medium 16765836

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas. The Journal of biological chemistry 250 19801672
2009 Disruption of ceramide synthesis by CerS2 down-regulation leads to autophagy and the unfolded protein response. The Biochemical journal 121 19728861
2012 miR-221 and miR-222 promote Schwann cell proliferation and migration by targeting LASS2 after sciatic nerve injury. Journal of cell science 114 22393241
2007 Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2. Histochemistry and cell biology 93 17901973
2012 LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump. Oncogene 85 22580606
2016 Enzyme Activities of the Ceramide Synthases CERS2-6 Are Regulated by Phosphorylation in the C-terminal Region. The Journal of biological chemistry 73 26887952
2015 miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 59 26150338
2015 CERS2 suppresses tumor cell invasion and is associated with decreased V-ATPase and MMP-2/MMP-9 activities in breast cancer. Journal of cellular biochemistry 57 25213553
2014 Silencing of LASS2/TMSG1 enhances invasion and metastasis capacity of prostate cancer cell. Journal of cellular biochemistry 39 24453046
2016 The asialoglycoprotein receptor suppresses the metastasis of hepatocellular carcinoma via LASS2-mediated inhibition of V-ATPase activity. Cancer letters 36 27241665
2012 Silencing of a novel tumor metastasis suppressor gene LASS2/TMSG1 promotes invasion of prostate cancer cell in vitro through increase of vacuolar ATPase activity. Journal of cellular biochemistry 36 22573553
2018 MicroRNA-98 promotes drug resistance and regulates mitochondrial dynamics by targeting LASS2 in bladder cancer cells. Experimental cell research 35 30463687
2014 A gene variant in CERS2 is associated with rate of increase in albuminuria in patients with diabetes from ONTARGET and TRANSCEND. PloS one 32 25238615
2015 AGPAT9 suppresses cell growth, invasion and metastasis by counteracting acidic tumor microenvironment through KLF4/LASS2/V-ATPase signaling pathway in breast cancer. Oncotarget 30 26110566
2016 Repression of the miR-93-enhanced sensitivity of bladder carcinoma to chemotherapy involves the regulation of LASS2. OncoTargets and therapy 28 27099514
2013 A novel tumor metastasis suppressor gene LASS2/TMSG1 interacts with vacuolar ATPase through its homeodomain. Journal of cellular biochemistry 28 22991218
2014 Renal sulfatides: sphingoid base-dependent localization and region-specific compensation of CerS2-dysfunction. Journal of lipid research 24 25267995
2014 LASS2/TMSG1 inhibits growth and invasion of breast cancer cell in vitro through regulation of vacuolar ATPase activity. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 25501280
2016 LASS2 inhibits growth and invasion of bladder cancer by regulating ATPase activity. Oncology letters 22 28356943
2018 LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells. Journal of Cancer 21 29581781
2013 Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis. Oncology reports 21 24337404
2013 Expression of a tumor-associated gene, LASS2, in the human bladder carcinoma cell lines BIU-87, T24, EJ and EJ-M3. Experimental and therapeutic medicine 17 23407876
2010 [LASS2 interacts with V-ATPase and inhibits cell growth of hepatocellular carcinoma]. Sheng li xue bao : [Acta physiologica Sinica] 17 20571735
2019 miR-3622a promotes proliferation and invasion of bladder cancer cells by downregulating LASS2. Gene 16 30898713
2017 Secretory pathway optimization of CHO producer cells by co-engineering of the mitosRNA-1978 target genes CerS2 and Tbc1D20. Metabolic engineering 16 28088541
2017 Silencing of vacuolar ATPase c subunit ATP6V0C inhibits the invasion of prostate cancer cells through a LASS2/TMSG1-independent manner. Oncology reports 16 29138865
2021 Targeting sphingosine kinase 1 (SK1) enhances oncogene-induced senescence through ceramide synthase 2 (CerS2)-mediated generation of very-long-chain ceramides. Cell death & disease 15 33414460
2019 Clinical and pathological significance of Homo sapiens ceramide synthase 2 (CerS-2) in diverse human cancers. Bioscience reports 15 30988071
2021 Characterizing a Common CERS2 Polymorphism in a Mouse Model of Metabolic Disease and in Subjects from the Utah CAD Study. The Journal of clinical endocrinology and metabolism 14 33705551
2018 Overexpression of LASS2 inhibits proliferation and causes G0/G1 cell cycle arrest in papillary thyroid cancer. Cancer cell international 14 30302058
2019 LASS2 inhibits proliferation and induces apoptosis in HepG2 cells by affecting mitochondrial dynamics, the cell cycle and the nuclear factor‑κB pathways. Oncology reports 13 30896811
2024 LASS2 suppresses metastasis in multiple cancers by regulating the ferroptosis signalling pathway through interaction with TFRC. Cancer cell international 12 38419028
2021 LASS2 mediates Nrf2-driven progestin resistance in endometrial cancer. American journal of translational research 11 33841656
2015 Overexpression of a Novel Tumor Metastasis Suppressor Gene TMSG1/LASS2 Induces Apoptosis via a Caspase-dependent Mitochondrial Pathway. Journal of cellular biochemistry 11 25735224
2024 Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease. Scientific reports 10 39080336
2021 Phosphorylated LASS2 inhibits prostate carcinogenesis via negative regulation of Wnt/β-catenin signaling. Journal of cellular biochemistry 10 33852174
2019 Evaluation of CERS2 Gene as a Potential Biomarker for Bladder Cancer. Disease markers 10 31636736
2018 Hsa-miR-3658 Promotes Cell Proliferation, Migration and Invasion by Effecting LASS2 in Bladder Cancer. Clinical laboratory 10 29739079
2022 Hsa-miR-221-3p promotes proliferation and migration in HER2-positive breast cancer cells by targeting LASS2 and MBD2. Histology and histopathology 9 35734966
2017 The role of LASS2 in regulating bladder cancer cell tumorigenicity in a nude mouse model. Oncology letters 9 29113153
2018 Hepatocyte-specific deletion of LASS2 protects against diet-induced hepatic steatosis and insulin resistance. Free radical biology & medicine 8 29626628
2025 Reduced circulating sphingolipids and CERS2 activity are linked to T2D risk and impaired insulin secretion. Science advances 7 39792658
2024 LASS2 enhances chemosensitivity to cisplatin by inhibiting PP2A-mediated β-catenin dephosphorylation in a subset of stem-like bladder cancer cells. BMC medicine 7 38191448
2021 MicroRNA-20a Targeting LASS2 Promotes the Proliferation, Invasiveness and Migration of Bladder Cancer. Clinical laboratory 7 34383404
2017 Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy. Biochemical and biophysical research communications 7 28958935
2022 LASS2 impairs proliferation of glioma stem cells and migration and invasion of glioma cells mainly via inhibition of EMT and apoptosis promotion. Journal of Cancer 6 35517425
2020 LASS2 regulates hepatocyte steatosis by interacting with NDUFS2/OXPHOS related proteins. Biochemical and biophysical research communications 5 32279995
2005 Expression of LASS2 controlled by LAG1 or ADH1 promoters cannot functionally complement Lag1p. Microbiological research 4 16765836
2023 LASS2 enhances p53 protein stability and nuclear import to suppress liver cancer progression through interaction with MDM2/MDMX. Cell death discovery 3 37963859
2022 LASS2 overexpression enhances early apoptosis of lung cancer cells through the caspase‑dependent pathway. Oncology reports 3 36300249
2024 Downregulation of CerS4 Instead of CerS2 in Liver Effectively Alleviates Hepatic Insulin Resistance in HFD Male Mice. Endocrinology 2 39233348
2020 Association of rs8444 polymorphism in the LASS2 3'-UTR and bladder cancer risk in Chinese population. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 2 31577563
2014 [LASS2/TMSG1 gene silencing promotes the invasiveness and metastatic of human prostatic carcinoma cells through increase in vacuolar ATPase activity]. Zhonghua bing li xue za zhi = Chinese journal of pathology 2 24842017
2025 Expression of LASS2 Can be Regulated by Dihydroartemisinin to Regulate Cisplatin Chemosensitivity in Bladder Cancer Cells. Current pharmaceutical biotechnology 1 38757331
2019 [Novel tumor metastasis suppressorgene LASS2/TMSG1 S248A mutant promotes invasion of prostate cancer cells through increasing ATP6V0C expression]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 1 30996356
2026 Discovery of a potential CERS2 inhibitor: hit compound identification via structure-based virtual screening and molecular dynamics simulations. Molecular diversity 0 41483315
2026 CerS2 is a druggable target in triple-negative breast cancer. Molecular cancer therapeutics 0 42012500
2025 CerS2 is a druggable target in triple-negative breast cancer. bioRxiv : the preprint server for biology 0 40894709
2025 [Effect of dephosphorylation of tumor metastasis suppressor gene LASS2 on vacuolar ATPase activity and invasiveness of prostate cancer]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 0 41399074
2023 [LASS2/TMSG1 overexpression inhibits proliferation and promotes apoptosis of human lung cancer A549 cells possibly by upregulating ceramide and p38 MAPK to activate a signaling cascade]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 36946034
2003 [Study of the expression membrane protein LASS2]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 0 15969039

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