title: Tumour-promoting role of SOCS1 in colorectal cancer cells.
abstract: The SOCS1 (Suppressor Of Cytokine Signalling 1) protein is considered a tumour suppressor. Notably, the SOCS1 gene is frequently silenced in cancer by hypermethylation of its promoter. Besides blocking inflammation, SOCS1 tumour suppressor activity involves Met receptor inhibition and enhancement of p53 tumour suppressor activity. However, the role of SOCS1 in colorectal cancer (CRC) remains understudied and controversial. Here, we investigated SOCS1 relevance for CRC by querying gene expression datasets of human CRC specimens from The Cancer Genome Atlas (TCGA), and by SOCS1 gain/loss-of-function analyses in murine and human colon carcinoma cells. Our results show that SOCS1 mRNA levels in tumours were more often elevated than reduced with respect to matched adjacent normal tissue of CRC specimens (n = 41). The analysis of TCGA dataset of 431 CRC patients revealed no correlation between SOCS1 expression and overall survival. Overexpression of SOCS1 in CRC cells triggered cell growth enhancement, anchorage-independent growth and resistance to death stimuli, whereas knockdown of SOCS1 reduced these oncogenic features. Moreover, SOCS1 overexpression in mouse CT26 cells increased tumourigenesis in vivo. Biochemical analyses showed that SOCS1 pro-oncogenic activity correlated with the down-modulation of STAT1 expression. Collectively, these results suggest that SOCS1 may work as an oncogene in CRC.
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: William S
authors.initials: WS
authors.lastname: Tobelaim
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Claudia
authors.initials: C
authors.lastname: Beaurivage
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Champagne
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Pomerleau
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Aline
authors.initials: A
authors.lastname: Simoneau
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Walid
authors.initials: W
authors.lastname: Chababi
authors.affiliation: Department of Pediatrics and Immunology division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yeganeh
authors.affiliation: Department of Microbiology and Infectiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Thibault
authors.affiliation: Department of Microbiology and Infectiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Carrier
authors.affiliation: Department of Biochemistry, Université de Montréal, Montréal, Quebec, H3C 3J7, Canada.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferbeyre
authors.affiliation: Department of Pediatrics and Immunology division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Subburaj
authors.initials: S
authors.lastname: Ilangumaran
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Saucier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; C108944:SOCS1 protein, human; D050794:STAT1 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016159:Tumor Suppressor Protein p53; D017228:Hepatocyte Growth Factor; D007371:Interferon-gamma