PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation

作者：Xiaojuan Wang, Fan Wu, Han Wang, Xiaoyuan Duan, R. Stephanie Huang, Amannisa Tuersuntuoheti, Luying Su, Shida Yan, Yuechao Zhao, Yan Lü, Kai Li, Jinjie Yao, Zhiwen Luo, Lei Guo, Jianmei Liu, Xiao Chen, Yalan Lu, Hanjie Hu, Xingchen Li, Mandula Bao, Xinyu Bi, Boyu Du, Shiying Miao, Jianqiang Cai, Linfang Wang, Haitao Zhou, Jianming Ying, Wei Song, Hong Zhao · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2020 · DOI：10.1186/s13046-020-01632-9 · 被引用次数：20 · 研究领域：Melanoma and MAPK Pathways、Endoplasmic Reticulum Stress and Disease、FOXO transcription factor regulation

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies, and it's expected that the CRC burden will substantially increase in the next two decades. New biomarkers for targeted treatment and associated molecular mechanism of tumorigenesis remain to be explored. In this study, we investigated whether PDCD6 plays an oncogenic role in colorectal cancer and its underlying mechanism. METHODS: Programmed cell death protein 6 (PDCD6) expression in CRC samples were analyzed by immunohistochemistry and immunofluorescence. The prognosis between PDCD6 and clinical features were analyzed. The roles of PDCD6 in cellular proliferation and tumor growth were measured by using CCK8, colony formation, and tumor xenograft in nude mice. RNA-sequence (RNA-seq), Mass Spectrum (MS), Co-Immunoprecipitation (Co-IP) and Western blot were utilized to investigate the mechanism of tumor progression. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were performed to determine the correlation of PDCD6 and MAPK pathway. RESULTS: Higher expression levels of PDCD6 in tumor tissues were associated with a poorer prognosis in patients with CRC. Furthermore, PDCD6 increased cell proliferation in vitro and tumor growth in vivo. Mechanistically, RNA-seq showed that PDCD6 could affect the activation of the MAPK signaling pathway. PDCD6 interacted with c-Raf, resulting in the activation of downstream c-Raf/MEK/ERK pathway and the upregulation of core cell proliferation genes such ...