RASAL2 promotes tumor progression through LATS2/YAP1 axis of hippo signaling pathway in colorectal cancer
Publication in refereed journal

替代計量分析
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其它資訊
摘要BACKGROUND:

Patients with colorectal cancer (CRC) have a high incidence of regional and distant metastases. Although metastasis is the main cause of CRC-related death, its molecular mechanisms remain largely unknown.

METHODS:

Using array-CGH and expression microarray analyses, changes in DNA copy number and mRNA expression levels were investigated in human CRC samples. The mRNA expression level of RASAL2 was validated by qRT-PCR, and the protein expression was evaluated by western blot as well as immunohistochemistry in CRC cell lines and primary tumors. The functional role of RASAL2 in CRC was determined by MTT proliferation assay, monolayer and soft agar colony formation assays, cell cycle analysis, cell invasion and migration and in vivo study through siRNA/shRNA mediated knockdown and overexpression assays. Identification of RASAL2 involved in hippo pathway was achieved by expression microarray screening, double immunofluorescence staining and co-immunoprecipitation assays.

RESULTS:

Integrated genomic analysis identified copy number gains and upregulation of RASAL2 in metastatic CRC. RASAL2 encodes a RAS-GTPase-activating protein (RAS-GAP) and showed increased expression in CRC cell lines and clinical specimens. Higher RASAL2 expression was significantly correlated with lymph node involvement and distant metastasis in CRC patients. Moreover, we found that RASAL2 serves as an independent prognostic marker of overall survival in CRC patients. In vitro and in vivo functional studies revealed that RASAL2 promoted tumor progression in both KRAS/NRAS mutant and wild-type CRC cells. Knockdown of RASAL2 promoted YAP1 phosphorylation, cytoplasm retention and ubiquitination, therefore activating the hippo pathway through the LATS2/YAP1 axis.

CONCLUSIONS:

Our findings demonstrated the roles of RASAL2 in CRC tumorigenesis as well as metastasis, and RASAL2 exerts its oncogenic property through LATS2/YAP1 axis of hippo signaling pathway in CRC.
出版社接受日期09.07.2018
著者Yi Pan, Joanna Hung Man Tong, Raymond Wai Ming Lung, Wei Kang, Johnny Sheung Him Kwan, Wing Po Chak, Ka Yee Tin, Lau Ying Chung, Feng Wu, Simon Siu Man Ng, Tony Wing Chung Mak, Jun Yu, Kwok Wai Lo, Anthony Wing Hung Chan, Ka Fai To
期刊名稱Molecular Cancer
出版年份2018
月份7
日期23
卷號17
期次1
出版社BIOMED CENTRAL LTD
文章號碼102
國際標準期刊號1476-4598
語言英式英語

上次更新時間 2021-14-10 於 23:45