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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2020

Open Access 01-12-2020 | Colorectal Cancer | Research

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

Authors: Xiaojuan Wang, Fan Wu, Han Wang, Xiaoyuan Duan, Rong Huang, Amannisa Tuersuntuoheti, Luying Su, Shida Yan, Yuechao Zhao, Yan Lu, 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

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2020

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Abstract

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 as MYC and JUN.

Conclusions

These findings reveal the oncogenic effect of PDCD6 in CRC by activating c-Raf/MEK/ERK pathway and indicate that PDCD6 might be a potential prognostic indicator and therapeutic target for patients with colorectal cancer.
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Metadata
Title
PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation
Authors
Xiaojuan Wang
Fan Wu
Han Wang
Xiaoyuan Duan
Rong Huang
Amannisa Tuersuntuoheti
Luying Su
Shida Yan
Yuechao Zhao
Yan Lu
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
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2020
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-020-01632-9

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