title: Decreased level of RASSF6 in sporadic colorectal cancer and its anti-tumor effects both in vitro and in vivo.
abstract: Ras-association domain family protein 6 (RASSF6) is a member of tumor suppressor RASSFs family with a wide range of function from RAS interaction, Hippo signaling involvement to cell cycle and apoptosis regulation. RASSF6 is reported inactivated in various types of cancer. However, whether RASSF6 is associated with colorectal cancer and the underlying mechanisms have yet to be investigated. In our previous exome sequencing study, we found a somatic loss-of-function (LoF) mutation in RASSF6 in one sporadic colorectal cancer (sCRC) patient, and two missense mutations in deep sequencing group of sCRC samples, implying the possibility that RASSF6 may be involved in the pathogenesis of sCRC. In this study, we demonstrate that RASSF6 acts as a tumor suppressor in colon cancer cells. Decreased level of RASSF6 was observed in adenocarcinoma compared to normal tissues, especially in advanced tumor cases. Further experiments showed exogenous introduction of RASSF6 into LoVo cells suppressed cell proliferation, migration, invasion, and induced apoptosis in vitro as well as tumor growth in vivo. In contrast, knockdown of RASSF6 in HT-29 cells showed the opposite effects. Taken together, our results suggest, in addition to epigenetics changes, functional somatic mutations may also contribute to the downregulation of RASSF6 and further participate in the pathogenesis of sCRC. RASSF6 may serve as a novel candidate against tumor growth for sCRC.
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.|Institute of Preventive Genomic Medicine, Xi'an, P.R. China.
authors.forename: Erfei
authors.initials: E
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.|Institute of Preventive Genomic Medicine, Xi'an, P.R. China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: He
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.|Institute of Preventive Genomic Medicine, Xi'an, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.|Institute of Preventive Genomic Medicine, Xi'an, P.R. China.
authors.forename: Ruitao
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.|Institute of Preventive Genomic Medicine, Xi'an, P.R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Du
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.|Institute of Preventive Genomic Medicine, Xi'an, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.|Institute of Preventive Genomic Medicine, Xi'an, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, P.R. China.|Institute of Preventive Genomic Medicine, Xi'an, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D034622:RNA Interference; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C519911:RASSF6 protein, human; D025521:Tumor Suppressor Proteins; D020559:Monomeric GTP-Binding Proteins
keywords: RASSF6; apoptosis; loss-of-function mutation; proliferation; sporadic colorectal cancer