title: RASSF10 is epigenetically silenced and functions as a tumor suppressor in gastric cancer.
abstract: Ras association domain family (RASSF) proteins are encoded by several tumor suppressor genes that are frequently silenced in human cancers. In this study, we investigated RASSF10 as a target of epigenetic inactivation and examined its functions as a tumor suppressor in gastric cancer. RASSF10 was silenced in six out of eight gastric cancer cell lines. Loss or downregulation of RASSF10 expression was associated with promoter hypermethylation, and could be restored by a demethylating agent. Overexpression of RASSF10 in gastric cancer cell lines (JRST, BGC823) suppressed cell growth and colony formation, and induced apoptosis, whereas RASSF10 depletion promoted cell growth. In xenograft animal experiments, RASSF10 overexpression effectively repressed tumor growth. Mechanistic investigations revealed that RASSF10 inhibited tumor growth by blocking activation of β-catenin and its downstream targets including c-Myc, cyclinD1, cyclinE1, peroxisome proliferator-activated receptor δ, transcription factor 4, transcription factor 1 and CD44. In conclusion, the results of this study provide insight into the role of RASSF10 as a novel functional tumor suppressor in gastric cancer through inhibition of the Wnt/β-catenin signaling pathway.
authors: Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors: Ziran
authors: Z
authors: Wei
authors: Xia
authors: X
authors: Chen
authors: Ji
authors: J
authors: Chen
authors: Weimin
authors: W
authors: Wang
authors: Xudong
authors: X
authors: Xu
authors: Qingping
authors: Q
authors: Cai
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: C548440:RASSF10 protein, human; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin