Dataset Information

SORBS2, mediated by MEF2D, suppresses the metastasis of human hepatocellular carcinoma by inhibitiing the c-Abl-ERK signaling pathway.

ABSTRACT: The RBP sorbin and SH3 domain-containing 2 (SORBS2) has been reported to be a tumor suppressor and is dysregulated in several cancer types. Nonetheless, the exact function and mechanism of action of SORBS2 in hepatocellular carcinoma (HCC) remain unclear. In this study, we found that expression levels of SORBS2 were significantly lower in HCC tissues than that in normal tissue samples, and underexpression of SORBS2 was associated with lower overall survival tates of patients with HCC. In HCC cell lines, SORBS2 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition, whereas SORBS2 inhibition yielded the opposite results. In vivo metastasis assays confirmed that overexpression of SORBS2 markedly inhibited HCC metastasis. Mechanistically, SORBS2 exerted tumor-suppressive effects on HCC by inhibiting the c-Abl/ERK signaling pathway. Furthermore, MEF2D, which binds to the promoter of SORBS2, was identified as an upstream regulator of SORBS2 and reduced SORBS2 expression. Our data suggest that SORBS2, downregulated by MEF2D, suppresses HCC metastasis through the c-Abl/ERK signaling pathway and has the potential to serve as a novel prognostic marker or therapeutic target in HCC.

SUBMITTER: Yan B

PROVIDER: S-EPMC6943356 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SORBS2, mediated by MEF2D, suppresses the metastasis of human hepatocellular carcinoma by inhibitiing the c-Abl-ERK signaling pathway.

Yan Bin B Peng Zhiyong Z Xing Chungen C

American journal of cancer research 20191201 12

The RBP sorbin and SH3 domain-containing 2 (SORBS2) has been reported to be a tumor suppressor and is dysregulated in several cancer types. Nonetheless, the exact function and mechanism of action of SORBS2 in hepatocellular carcinoma (HCC) remain unclear. In this study, we found that expression levels of SORBS2 were significantly lower in HCC tissues than that in normal tissue samples, and underexpression of SORBS2 was associated with lower overall survival tates of patients with HCC. In HCC cel ...[more]

PMID: 31911856

Similar Datasets

Project description:BackgroundThe role of the membrane-associated RING-CH (MARCH) family in carcinogenesis has been widely studied, but the member of this family, RNF173, has not yet been thoroughly explored in the context of hepatocellular carcinoma (HCC).MethodsWith the use of an HCC tissue microarray and IHC staining, we aim to determine the differential expression of RNF173 in HCC patients and its clinical significance. The biological role of RNF173 is investigated through in vitro and in vivo experiments. RNA sequencing, mass spectrometry, and immunoprecipitation are performed to uncover the underlying mechanism of RNF173's impact on the development of HCC.ResultsThe mRNA and protein levels of RNF173 were significantly lower in HCC tissues than in normal tissues. HCC patients with low RNF173 expression had shorter overall survival and recurrence-free survival, and RNF173 was significantly correlated with tumor number, tumor capsule, tumor differentiation, and BCLC stage. In addition, in vitro and in vivo experiments showed that RNF173 downregulation exacerbated tumor progression, including migration, invasion, and proliferation. GRB2 is a key molecule in the RAF/MEK/ERK pathway. RNF173 inhibits the RAF/MEK/ERK signaling by ubiquitinating and degrading GRB2, thereby suppressing HCC cell proliferation, invasion and migration. Combining clinical samples, we found that HCC patients with high RNF173 and low GRB2 expression had the best prognosis.ConclusionRNF173 inhibits the invasion and metastasis of HCC by ubiquitinating and degrading GRB2, thereby suppressing the RAF/MEK/ERK signaling pathway. RNF173 is an independent risk factor for the survival and recurrence of HCC patients. RNF173 may serve as a novel prognostic molecule and potential therapeutic target for HCC. Video Abstract Graphical abstract Model of RNF173 on RAF/MEK/ERK signaling. RNF173 knockdown resulted in impaired ubiquitination and degradation of GRB2, leading to the activation of the RAF/MEK/ERK signaling pathway and promotion of invasion and metastasis in HCC cells.

Dataset Information

SORBS2, mediated by MEF2D, suppresses the metastasis of human hepatocellular carcinoma by inhibitiing the c-Abl-ERK signaling pathway.

Publications

SORBS2, mediated by MEF2D, suppresses the metastasis of human hepatocellular carcinoma by inhibitiing the c-Abl-ERK signaling pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets