ArticlePloS one2012
The insulin receptor substrate 1 (IRS1) in intestinal epithelial differentiation and in colorectal cancer.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- The tumour biology of synchronous and metachronous colorectal liver metastases: a systematic review.Clinical & experimental metastasis · 2013Pooled it
- Single nucleotide polymorphisms in the IGF-IRS pathway are associated with outcome in mCRC patients enrolled in the FIRE-3 trial.International journal of cancer · 2017Trial
- Evaluation of EGFR and COX pathway inhibition in human colon organoids of serrated polyposis and other hereditary cancer syndromes.Familial cancer · 2024Article
- Human cytomegalovirus infection enhances 5‑lipoxygenase and cycloxygenase‑2 expression in colorectal cancer.International journal of oncology · 2023Article
- Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases.Biomedicines · 2023Review
- Overexpression of Insulin Receptor Substrate 1 (IRS1) Relates to Poor Prognosis and Promotes Proliferation, Stemness, Migration, and Oxidative Stress Resistance in Cholangiocarcinoma.International journal of molecular sciences · 2023Article
- Hippo pathway in intestinal diseases: focusing on ferroptosis.Frontiers in cell and developmental biology · 2023Review
- The Novel IGF-1R Inhibitor PB-020 Acts Synergistically with Anti-PD-1 and Mebendazole against Colorectal Cancer.Cancers · 2022Article
- The Insulin-like Growth Factor System and Colorectal Cancer.Life (Basel, Switzerland) · 2022Review
- Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents.International journal of molecular sciences · 2021Review
- Genome-wide CRISPR-Cas9 screening identifies that hypoxia-inducible factor-1a-inducedWorld journal of gastrointestinal oncology · 2021Article
- Obesity and intestinal stem cell susceptibility to carcinogenesis.Nutrition & metabolism · 2021Review
- The role of immune dysfunction in obesity-associated cancer risk, progression, and metastasis.Cellular and molecular life sciences : CMLS · 2021Review
- Review
- Downregulation of microRNA-126 is inversely correlated with insulin receptor substrate-1 protein expression in colorectal cancer and is associated with advanced stages of disease.Oncology letters · 2020Article
- Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression.World journal of gastroenterology · 2020Article
- Single-cell lineage analysis reveals genetic and epigenetic interplay in glioblastoma drug resistance.Genome biology · 2020Article
- Integrative Analysis of the Genes Induced by the Intestine Microbiota of Infant Born to Term and Breastfed.Bioinformatics and biology insights · 2020Article
- Role of anabolic agents in colorectal carcinogenesis: Myths and realities (Review).Oncology reports · 2019Review
- MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1) is a key transducer. We investigated expression, localization and pathologic correlations of IRS1 in cancer-uninvolved colonic epithelium, primary CRCs with paired liver metastases and in vitro polarizing Caco2 and HT29 cells. IRS1 mRNA and protein resulted higher, relative to paired mucosa, in adenomas of familial adenomatous polyposis patients and in CRCs that overexpressed c-MYC, ß-catenin, InsRß, and IGF1R. Analysis of IRS1 immunostaining in 24 cases of primary CRC with paired colonic epithelium and hepatic metastasis showed that staining intensity was significantly higher in metastases relative to both primary CRC (P<0.01) and colonic epithelium (P<0.01). Primary and metastatic CRCs, compared to colonic epithelium, contained significantly higher numbers of IRS1-positive cells (P = 0.013 and P = 0.014, respectively). Pathologic correlations in 163 primary CRCs revealed that diffuse IRS1 staining was associated with tumors combining differentiated phenotype and aggressive markers (high Ki67, p53, and ß-catenin). In Caco 2 IRS1 and InsR were maximally expressed after polarization, while IGF1R was highest in pre-polarized cells. No nuclear IRS1 was detected, while, with polarization, phosphorylated IRS1 (pIRS1) shifted from the lateral to the apical plasma membrane and was expressed in surface cells only. In HT29, that carry mutations constitutively activating survival signaling, IRS1 and IGF1R decreased with polarization, while pIRS1 localized in nuclear spots throughout the course. Overall, these data provide evidence that IRS1 is modulated according to CRC differentiation, and support a role of IRS1 in CRC progression and liver metastatization.
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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.