p130Cas Is Correlated with EREG Expression and a Prognostic Factor Depending on Colorectal Cancer Stage and Localization Reducing FOLFIRI Efficacy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34830244", "kind": "science-record", "revision": 4, "content_hash": "sha256:21cab210112d6ff31a19983a655e60d95ec2b84304b719a5205727e466004bff", "created_at": "2026-11-01T17:36:32Z", "updated_at": "2026-11-01T22:47:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "p130Cas Is Correlated with EREG Expression and a Prognostic Factor Depending on Colorectal Cancer Stage and Localization Reducing FOLFIRI Efficacy.", "doi": "10.3390/ijms222212364", "pmid": "34830244", "authors": ["Jörg Kumbrink", "Pan Li", "Agnes Pók-Udvari", "Frederick Klauschen", "Thomas Kirchner", "Andreas Jung"], "journal": "International journal of molecular sciences", "year": 2021, "abstract": "p130 Crk-associated substrate (p130Cas) is associated with poor prognosis and treatment resistance in breast and lung cancers. To elucidate p130Cas functional and clinical role in colorectal cancer (CRC) progression/therapy resistance, we performed cell culture experiments and bioinformatic/statistical analyses of clinical data sets. p130Cas expression was associated with poor survival in the cancer genome atlas (TCGA) data set. Knockdown/reconstitution experiments showed that p130Cas drives migration but, unexpectedly, inhibits proliferation in CRC cells. TCGA data analyses identified the growth factor epiregulin (EREG) as inversely correlated with p130Cas. p130Cas knockdown and simultaneous EREG treatment further enhanced proliferation. RNA interference and EREG treatment experiments suggested that p130Cas/EREG limit each other's expression/activity. Inverse p130Cas/EREG Spearman correlations were prominent in right-sided and earlier stage CRC. p130Cas was inducible by 5-fluorouracil (5-FU) and FOLFIRI (folinic acid, 5-FU, irinotecan), and p130Cas and EREG were upregulated in distant metastases (GSE121418). Positive p130Cas/EREG correlations were observed in metastases, preferentially in post-treatment samples (especially pulmonary metastases). p130Cas knockdown sensitized CRC cells to FOLFIRI independent of EREG treatment. RNA sequencing and gene ontology analyses revealed that p130Cas is involved in cytochrome P450 drug metabolism and epithelial-mesenchymal transition. p130Cas expression was associated with poor survival in right-sided, stage I/II, MSS (microsatellite stable), or BRAF-mutated CRC. In summary, p130Cas represents a prognostic factor and potential therapeutic target in CRC.", "claims": [{"id": "claim-method", "statement": "Overall survival (OS) was estimated with the Kaplan–Meier method and compared with logrank test (ggplot2 and survival R packages). The effect of molecular markers was estimated with the Cox proportional hazards model (survminer R package).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34830244", "locator": "sections[20] \"4.8. Data Sources and Statistical Analyses\" paragraph 3", "quote": "Overall survival (OS) was estimated with the Kaplan–Meier method and compared with logrank test (ggplot2 and survival R packages). The effect of molecular markers was estimated with the Cox proportional hazards model (survminer R package)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The RNA sequencing data presented in this study are available on request from the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34830244", "locator": "sections[28] \"notes\" paragraph 1", "quote": "The RNA sequencing data presented in this study are available on request from the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Higher BCAR1 levels were significantly associated with reduced survival in the CoAd cohort.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Indeed, higher BCAR1 levels were significantly associated with reduced survival in the CoAd cohort (BCAR1 high: n = 252; BCAR1 low: n = 336; p = 0.02, HR = 1.535 (95%CI 1.071–2.201)) (Figure 1B)."}, "evidence": [{"asset": "source:pmid:34830244", "locator": "sections[3] \"2.1. 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