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

// Fei Miao 1 , Mengmeng Zhang 1 , Yuechao Zhao 1 , Xiaolu Li 1 , Rongyan Yao 1 , Fan Wu 1 , Rong Huang 1 , Kai Li 1 , Shiying Miao 1 , Changwu Ma 4 , Hongge Ju 2, 3 , Wei Song 1 , Linfang Wang 1 1 Department 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 2 Department of Pathology, Baotou Medical College, Baotou 014040, China 3 Department of Pathology, The First Affiliated Hospital of Baotou Medical College, Baotou 014010, China 4 Department of Medical Oncology, Chifeng Municipal Hospital, Chifeng 024000, China Correspondence to: Changwu Ma, email: docmachangwu@126.com Hongge Ju, email: juhongge1088@163.com Wei Song, email: songwei@ibms.pumc.edu.cn 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.