title: Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells.
abstract: Suppressor of cytokine signaling (SOCS) 1 is an inducible negative regulator of cytokine signaling but its role in human cancer is not completely established. Here we report that, while SOCS1 is expressed in normal colonic epithelium and colon adenocarcinomas, its level decreases during progression of colon adenocarcinomas, the lowest level being found in the most aggressive stage and least differentiated carcinomas. Forced expression of SOCS1 in metastatic colorectal SW620 cells reverses many characteristics of Epithelial-Mesenchymal Transition (EMT), as highlighted by the disappearance of the transcription factor ZEB1 and the mesenchymal form of p120ctn and the re-expression of E-cadherin. Furthermore, miRNA profiling indicated that SOCS1 also up-regulates the expression of the mir-200 family of miRNAs, which can promote the mesenchymal-epithelial transition and reduce tumor cell migration. Accordingly, overexpression of SOCS1 induced cell morphology changes and dramatically reduced tumor cell invasion in vitro. When injected in nude mice, SOCS1-expressing SW620 cells induced metastases in a smaller number of animals than parental SW620 cells, and did not generate any adrenal gland or bone metastasis. Overall, our results suggest that SOCS1 controls metastatic progression of colorectal tumors by preventing the mesenchymal-epithelial transition (MET), including E-cadherin expression. This pathway may be associated with survival to colorectal cancer by reducing the capacity of generating metastases.
authors.affiliation: INSERM U749, Institut Gustave Roussy, 39, Rue Camille Desmoulins, 94800 Villejuif, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: David
authors.affiliation: CNRS UMR5237, CRBM, 1919 route de Mende, Montpellier, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Naudin
authors.affiliation: INSERM U749, Institut Gustave Roussy, 39, Rue Camille Desmoulins, 94800 Villejuif, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Letourneur
authors.affiliation: Preclinical Evaluation Platform (PFEP), Institut Gustave Roussy, 39, Rue Camille Desmoulins, 94800 Villejuif, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Polrot
authors.affiliation: INSERM U749, Institut Gustave Roussy, 39, Rue Camille Desmoulins, 94800 Villejuif, France.
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
authors.affiliation: Genomic Unit, Institut Gustave Roussy, 39, Rue Camille Desmoulins, 94800 Villejuif, France.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.affiliation: Genomic Unit, Institut Gustave Roussy, 39, Rue Camille Desmoulins, 94800 Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.affiliation: CNRS UMR5237, CRBM, 1919 route de Mende, Montpellier, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Roche
authors.affiliation: INSERM U749, Institut Gustave Roussy, 39, Rue Camille Desmoulins, 94800 Villejuif, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bertoglio
authors.affiliation: INSERM U749, Institut Gustave Roussy, 39, Rue Camille Desmoulins, 94800 Villejuif, France. Electronic address: josiane.pierre@gustaveroussy.fr.
authors.forename: Josiane
authors.initials: J
authors.lastname: Pierre
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D012007:Rectum / Q000378:metabolism / Q000473:pathology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D015820:Cadherins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: Colorectal cancer; Invasion; Metastasis; SOCS1
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