ArticleJournal of experimental & clinical cancer research : CR2022
Genome-wide CRISPR/Cas9 library screen identifies PCMT1 as a critical driver of ovarian cancer metastasis.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Unraveling the role of M2 TAMs in ovarian cancer dynamics: a systematic review.Journal of translational medicine · 2025Pooled it
- Mitochondrial Localization of Cx26 Promotes Colorectal Cancer Malignancy and Exposes a Fatal Vulnerability to Drug Targeting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LAMB3 drives gastric cancer progression through SAMD4A-mediated degradation of PHLPP2 mRNA leading to sustained PI3K-Akt activation.British journal of cancer · 2026Article
- Detachment-Induced FAK-STAT3-NNMT Inhibits CTCs Anoikis to Promote Breast Cancer Metastasis by Enhancing Fatty Acid Oxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Harnessing Anoikis-Related Gene Signatures for Immunotherapy Precision: A Machine Learning-Driven Predictive and Prognostic Model.ACS omega · 2026Article
- The role of PCMT1 in prognosis tumor immune microenvironment and therapeutic responses across cancers.Discover oncology · 2026Article
- LITAF suppresses breast cancer and paclitaxel resistance by ubiquitinating and degrading PCMT1 to inhibit COX-2-dependent arachidonic acid metabolism.Frontiers in pharmacology · 2026Article
- Long noncoding RNA BMPR1B-DT promotes anoikis and reduces proliferation in ovarian cancer.BMC cancer · 2025Article
- Cross-cohort integrative multi-omics analysis of cancer essential gene ATP6V0B to dissect functional characteristics and clinical implications in breast cancer.World journal of surgical oncology · 2025Article
- Revealing genetic drivers of ovarian cancer and chemoresistance: insights from whole-genome CRISPR-knockout library screens.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Mechanisms Involved in Focal Adhesion Signaling Regulating Tumor Anoikis Resistance.Cancer science · 2025Review
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Multi-omics Analysis Sheds Light on the Extracellular Role of PCMT1.Journal of proteome research · 2025Article
- PCMT1 as a prognostic marker in breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Circular RNA circCLASP2 promotes nasopharyngeal carcinoma progression through binding to DHX9 to enhance PCMT1 translation.Molecular cancer · 2025Article
- Repair of Isoaspartyl Residues by PCMT1 and Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2025Article
- BRPF1 inhibition reduces migration and invasion of metastatic ovarian cancer cells, representing a potential therapeutic target.Scientific reports · 2025Article
- SPTLC2 drives an EGFR-FAK-HBEGF signaling axis to promote ovarian cancer progression.Oncogene · 2025Article
- Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.International journal of molecular sciences · 2025Article
- Tumor Microenvironment Responsive Key Nanomicelles for Effective Against Invasion and Metastasis in Ovarian Cancer Using Mice Model.International journal of nanomedicine · 2025Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe development of lethal cancer metastasis depends on the dynamic interactions between cancer cells and the tumor microenvironment, both of which are embedded in the extracellular matrix (ECM). The acquisition of resistance to detachment-induced apoptosis, also known as anoikis, is a critical step in the metastatic cascade. Thus, a more in-depth and systematic analysis is needed to identify the key drivers of anoikis resistance.
methodsGenome-wide CRISPR/Cas9 knockout screen was used to identify critical drivers of anoikis resistance using SKOV3 cell line and found protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) as a candidate. Quantitative real-time PCR (qRT-PCR) and immune-histochemistry (IHC) were used to measure differentially expressed PCMT1 in primary tissues and metastatic cancer tissues. PCMT1 knockdown/knockout and overexpression were performed to investigate the functional role of PCMT1 in vitro and in vivo. The expression and regulation of PCMT1 and integrin-FAK-Src pathway were evaluated using immunoprecipitation followed by mass spectrometry (IP-MS), western blot analysis and live cell imaging.
resultsWe found that PCMT1 enhanced cell migration, adhesion, and spheroid formation in vitro. Interestingly, PCMT1 was released from ovarian cancer cells, and interacted with the ECM protein LAMB3, which binds to integrin and activates FAK-Src signaling to promote cancer progression. Strikingly, treatment with an antibody against extracellular PCMT1 effectively reduced ovarian cancer cell invasion and adhesion. Our in vivo results indicated that overexpression of PCMT1 led to increased ascites formation and distant metastasis, whereas knockout of PCMT1 had the opposite effect. Importantly, PCMT1 was highly expressed in late-stage metastatic tumors compared to early-stage primary tumors.
conclusionsThrough systematically identifying the drivers of anoikis resistance, we uncovered the contribution of PCMT1 to focal adhesion (FA) dynamics as well as cancer metastasis. Our study suggested that PCMT1 has the potential to be a therapeutic target in metastatic ovarian cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.