Oncotarget

Research Papers:

RHBDD1 upregulates EGFR via the AP-1 pathway in colorectal cancer

Fei Miao, Mengmeng Zhang, Yuechao Zhao, Xiaolu Li, Rongyan Yao, Fan Wu, Rong Huang, Kai Li, Shiying Miao, Changwu Ma _, Hongge Ju, Wei Song and Linfang Wang

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Oncotarget. 2017; 8:25251-25260. https://doi.org/10.18632/oncotarget.15694

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Abstract

Fei Miao1, Mengmeng Zhang1, Yuechao Zhao1, Xiaolu Li1, Rongyan Yao1, Fan Wu1, Rong Huang1, Kai Li1, Shiying Miao1, Changwu Ma4, Hongge Ju2,3, Wei Song1, Linfang Wang1

1Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China

2Department of Pathology, Baotou Medical College, Baotou 014040, China

3Department of Pathology, The First Affiliated Hospital of Baotou Medical College, Baotou 014010, China

4Department of Medical Oncology, Chifeng Municipal Hospital, Chifeng 024000, China

Correspondence to:

Changwu Ma, email: [email protected]

Hongge Ju, email: [email protected]

Wei Song, email: [email protected]

Keywords: colorectal cancer, EGFR, RHBDD1, AP-1, c-Jun

Received: September 02, 2016     Accepted: January 24, 2017     Published: February 25, 2017

ABSTRACT

Our previous study showed that RHBDD1 can activate the EGFR signaling pathway to promote colorectal cancer growth. In the present study, EGFR was decreased when RHBDD1 was knocked down or inactivated. Further analysis found that c-Jun and EGFR protein expression was decreased in RHBDD1 knockdown and inactivated cells. c-Jun overexpression in RHBDD1-inactivated cells rescued EGFR expression in a dose-dependent manner. RHBDD1 overexpression in RHBDD1-inactivated cells restored EGFR expression, but this effect was counteracted by c-Jun knockdown. Furthermore, EGFR and c-Jun were attenuated in the RHBDD1 knockdown and inactivated groups in animal tumor models. Tissue microarray assays demonstrated a correlation between RHBDD1 and EGFR in colorectal cancer patients. Therefore, our findings indicate that RHBDD1 stimulates EGFR expression by promoting the AP-1 pathway.


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