Theme：Targeting the androgen-regulated unfolded protein response in prostate cancer

Host：Dr. Xia Sheng

Time：15th May, 2020, 10:00-11:40

Location: Zoom 

Abstract: 

The endoplasmic reticulum (ER) not only plays a central role in maintaining proteostasis, but also contributes to other key biological processes, including Ca2+ metabolism and the synthesis of lipids and glucose. Stress conditions, such as shortage in glucose or oxygen and disruption of Ca2+ homeostasis, may perturb proteostasis and induce the unfolded protein response (UPR), which either restores homeostasis or triggers cell death. Crucial roles of UPR signaling have been implicated in various cancers, from oncogenesis to treatment response. We show that androgens activate IRE1α-XBP1s while repress PERK-eIF2α signaling in prostate cancer. We further report that an IRE1α RNase inhibitor suppresses tumor initiation and progression in response to mild ER stress, and exhibits synergistic antitumor effects in vivo when combined with clinically approved drugs. Mechanistically, XBP1s may transcriptionally induce MYC expression and activate c-Myc signaling. Building on these findings as well as other recent developments, targeting key UPR signaling nodes has emerged as novel synthetic lethal strategies in MYC-driven cancers.

Biography: 

Xia Sheng is an associate professor at the School of Public Health, Huazhong University of Science and Technology since March 2018. He got his master’s degree at Beijing Forestry University in 2012. In 2016, he received his Ph.D. at University of Oslo, Norway, where he continued his postdoctoral training until 2018.Dr. Sheng has been interested in studying the role of endoplasmic reticulum stress and unfolded protein response in the initiation and development of diseases. He uncovered the divergent regulation of the UPR pathways by androgens in prostate cancer, and the direct activation of Myc oncogenic signaling by IRE1-XBP1 therein. These findings, together with others, suggested that UPR may be a synthetic lethal target in Myc-driven cancers. In the past 5 years, Dr. Sheng has published 20 scientific articles in journals including Nature Communications, EMBO Molecular Medicine, and Environment International.