title: Insulin-induced gene 2 expression correlates with colorectal cancer metastasis and disease outcome.
abstract: Colorectal cancer (CRC) is one of the most common cancers worldwide accounting for ∼9% of cancer-related deaths, 90% of which are due to metastasis resulting from resistance to chemotherapeutic agents. Hence, it is imperative to develop novel biomarkers of CRC. Insulin-induced gene 2 (INSIG2) has been previously reported to be a negative regulator of cholesterol synthesis and was recently identified as a putative-positive prognostic biomarker for colon and pancreatic cancer prognosis. Even though it has been suggested as a colon cancer biomarker and as an inhibitor of Bax-mediated apoptosis, the role of INSIG2 in CRC is elusive. We initially validated that INSIG2 is a gene with univariate-negative prognostic capacity to discriminate human colon cancer survivorship and that if present along with adenomatous polyposis coli (APC) gene mutations further decrease overall survival. Gain- and loss-of-function studies of INSIG2 showed that the gene product is responsible for inducing migration and invasion and maintenance of the mesenchymal phenotype in vitro and metastasis in vivo. Interestingly, loss of INSIG2 did not affect tumorigenic potential per se, but affected hepatic invasion in a xenograft assay. Our findings reinforce that INSIG2 is a novel colon cancer biomarker, and suggest, for the first time, an exclusive connection between INSIG2 and metastatic dissemination without any effect on tumorigenesis. © 2015 IUBMB Life, 68(1):65-71, 2016.
authors.affiliation: Department of Oncology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Oncology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Oncology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Oncology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Oncology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Oncology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Oncology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D063646:Carcinogenesis / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015870:Gene Expression; D019073:HT29 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016016:Proportional Hazards Models
chemical_list: C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins
keywords: EMT; biomarker; colorectal cancer; insulin-induced gene 2