Journal Article

The endoplasmic reticulum stress response in prostate cancer

Shee, Kevin, Yang, Heiko, de la Calle, Claire M, Lonergan, Peter E, Nguyen, Hao G

2022

Overview

In order to proliferate in unfavourable conditions, cancer cells can take advantage of the naturally occurring endoplasmic reticulum-associated unfolded protein response (UPR) via three highly conserved signalling arms: IRE1α, PERK and ATF6. All three arms of the UPR have key roles in every step of tumour progression: from cancer initiation to tumour growth, invasion, metastasis and resistance to therapy. At present, no cure for metastatic prostate cancer exists, as targeting the androgen receptor eventually results in treatment resistance. New research has uncovered an important role for the UPR in prostate cancer tumorigenesis and crosstalk between the UPR and androgen receptor signalling pathways. With an improved understanding of the mechanisms by which cancer cells exploit the endoplasmic reticulum stress response, targetable points of vulnerability can be uncovered.The unfolded protein response has an important role in prostate cancer tumorigenesis. Here, the authors discuss its involvement in prostate cancer development and progression, interactions with androgen receptor signalling, and the therapeutic implications for the treatment of metastatic disease.

• Publisher: Nature Publishing Group
• Subject: Androgens / Endoplasmic reticulum / Metastasis / Prostate cancer / Treatment resistance / Tumorigenesis