ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30063110", "kind": "science-record", "revision": 6, "content_hash": "sha256:0696ca9e58495d241574aa41b43801ef6e4d89d2405f193d309d3afba2a74744", "created_at": "2026-11-01T15:40:36Z", "updated_at": "2026-11-01T21:21:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer.", "doi": "10.1002/1878-0261.12365", "pmid": "30063110", "authors": ["Chun-Yu Liu", "Chia-Chi Hsu", "Tzu-Ting Huang", "Chia-Han Lee", "Ji-Lin Chen", "Shung-Haur Yang", "Jeng-Kai Jiang", "Wei-Shone Chen", "Kuan-Der Lee", "Hao-Wei Teng"], "journal": "Molecular oncology", "year": 2018, "abstract": "Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress-related ATF signaling and CIP2A. We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA). In addition, we demonstrated that tunicamycin-induced ER stress in vitro upregulated ATF6 and CIP2A. Mechanistically, we found that ATF6 directly bound to the CIP2A promoter and induced CIP2A gene expression, which contributed to colon cancer cell survival. Furthermore, knockdown of CIP2A reduced the viability of cells under ER stress. Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis. Taken together, our results show that ER stress-related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer. Targeting CIP2A may disrupt ER stress-mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer.", "claims": [{"id": "claim-method", "statement": "The correlation between KIAA1524 and ATF6 was analyzed using Pearson and Spearman's correlation tests, respectively (A).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30063110", "locator": "sections[17] \"CIP2A expression positively correlates with ATF6 expression in both clinical specimens and with ER stress in vitro\" paragraph 3", "quote": "The correlation between KIAA1524 and ATF6 was analyzed using Pearson and Spearman's correlation tests, respectively (A)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "To examine the relationship between ATF6 and CIP2A, we downloaded The Cancer Genome Atlas (TCGA) data from the cBioPortal website (http://www.cbioportal.org/) (Cerami et al., 2012; Gao et al., 2013) and analyzed the correlation between ATF6 and CIP2A gene expression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30063110", "locator": "sections[17] \"CIP2A expression positively correlates with ATF6 expression in both clinical specimens and with ER stress in vitro\" paragraph 2", "quote": "To examine the relationship between ATF6 and CIP2A, we downloaded The Cancer Genome Atlas (TCGA) data from the cBioPortal website (http://www.cbioportal.org/) (Cerami et al., 2012; Gao et al., 2013) and analyzed the correlation between ATF6 and CIP2A gene expression."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The headline result was that ER stress–related ATF6 upregulates CIP2A, contributes to colon cancer cell survival and poor prognosis, and may represent a therapeutic target. Statistical analyses used nonparametric tests, χ2 or Fisher’s exact tests for clinicopathological associations, Kaplan–Meier survival estimates, and a two-sided significance threshold of P < 0.05. The source-data routes were publicly available TCGA RNA-sequence data accessed through cBioPortal and a colon cancer patient cohort analyzed by tissue-microarray immunohistochemistry.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Data are expressed as mean ± SD or SE. Statistical comparisons were based on nonparametric tests, and statistical significance was defined at P < 0.05."}, "evidence": [{"asset": "source:pmid:30063110", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Taken together, our results show that ER stress‐related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer."}, {"asset": "source:pmid:30063110", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Targeting CIP2A may disrupt ER stress‐mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer."}, {"asset": "source:pmid:30063110", "locator": "sections[15] \"Statistical and survival analysis\" paragraph 2", "quote": "Data are expressed as mean ± SD or SE. Statistical comparisons were based on nonparametric tests, and statistical significance was defined at P < 0.05."}, {"asset": "source:pmid:30063110", "locator": "sections[15] \"Statistical and survival analysis\" paragraph 2", "quote": "The correlations between clinicopathological variables and immunopositivity were analyzed using the χ2 test or Fisher's exact test."}, {"asset": "source:pmid:30063110", "locator": "sections[15] \"Statistical and survival analysis\" paragraph 2", "quote": "Survival was estimated using the Kaplan–Meier method."}, {"asset": "source:pmid:30063110", "locator": "sections[15] \"Statistical and survival analysis\" paragraph 2", "quote": "A two‐sided P value of < 0.05 was regarded as statistically significant."}, {"asset": "source:pmid:30063110", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA)."}, {"asset": "source:pmid:30063110", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The headline result was that ER stress–related ATF6 upregulates CIP2A, contributes to colon cancer cell survival and poor prognosis, and may represent a therapeutic target. Statistical analyses used nonparametric tests, χ2 or Fisher’s exact tests for clinicopathological associations, Kaplan–Meier survival estimates, and a two-sided significance threshold of P < 0.05. The source-data routes were publicly available TCGA RNA-sequence data accessed through cBioPortal and a colon cancer patient cohort analyzed by tissue-microarray immunohistochemistry.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30063110"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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