BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia

Hongmei Li; Can Zhang; Qiong Zhang; Jiezhi Jia; Xiaojiao Wang

doi:10.1016/j.heliyon.2022.e11190

BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia

Heliyon. 2022 Oct 20;8(10):e11190. doi: 10.1016/j.heliyon.2022.e11190. eCollection 2022 Oct.

Authors

Hongmei Li¹, Can Zhang², Qiong Zhang³, Jiezhi Jia³, Xiaojiao Wang¹

Affiliations

¹ Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
² Department of Plastic Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
³ Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

Abstract

Chemotherapy and immunotherapy for pancreatic ductal adenocarcinoma (PDAC) have limited success for the intricated surrounding cancer microenvironment. Hypoxic microenvironment in PDAC causes the activation of multiple different molecules and signaling pathways compared with normoxia. We studied the roles of BNIP3 for the migration and proliferation of PDAC and Panc1 cells in vitro. In the present study, we found that BNIP3 expression was elevated and enhanced the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. The upregulation of BNIP3 was important for the autophagic activation, while inhibition of autophagy with siRNA targeting Atg5 and Atg7 impaired the hypoxia-induced cell migration and proliferation. Additionally, blocking ERK1/2 mitogen-activated protein kinase (MAPK) signaling with PD98058 significantly down-regulated BNIP3 expression, autophagic activation, as well as the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. Collectively, our results here uncover a hitherto unknown hypoxia-BNIP3-autophagy axis in modulating the migration and proliferation and provide a potential intriguing drug target for the therapy of PDAC.

Keywords: Autophagy; BNIP3; ERK1/2; Hypoxia; Pancreatic ductal adenocarcinoma.