title: Ras-association domain family 10 acts as a novel tumor suppressor through modulating MMP2 in hepatocarcinoma.
abstract: Ras-Association Domain Family 10 (RASSF10) is the last identified member of the RASSF family. The functional characteristics of this new gene in human cancers remain largely unclear. Here, we examined RASSF10 for the biological functions and related molecular mechanisms in hepatocellular carcinoma (HCC). We found that RASSF10 is expressed in normal human liver tissue, but is silenced or down-regulated in 62.5% (5/8) of HCC cell lines. The mean expression level of RASSF10 was significantly lower in primary HCCs compared with their adjacent normal tissues (P<0.005, n=52). The promoter methylation contributes to the inactivation of RASSF10 as demonstrated by bisulfite genomic sequencing and demethylation treatment analyses. Transgenic expression of RASSF10 in silenced HCC cell lines suppressed cell viability, colony formation and inhibited tumor growth in nude mice (QGY7703, P<0.01; HepG2, P<0.05). Furthermore, RASSF10 was shown to induce the cell accumulation in G1 phase with the increase of p27, as well as the decrease of cyclinD1 and CDK2/CDK4. Over-expression of RASSF10 also inhibited HCC cells migration (P<0.01) or invasion (P<0.05). Adhesion genes array revealed that Matrix Metalloproteinase 2 (MMP2) was a downstream effector of RASSF10. RASSF10 acting as a tumor suppressor to inhibit HCC invasion partially mediated by Focal Adhesion Kinase or p38 MAPK to decrease the accumulation of MMP2. Our study suggests that RASSF10 acts as a tumor suppressor for HCC.
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Postgraduate at Institute of Gastroenterology, Zhejiang University; The First People's Hospital of Xiaoshan, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Qian
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Xuan
authors.affiliation: Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhuo
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: X
authors.identifier: http://orcid.org/0000-0001-8791-7505
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Si