Loss of ATF6α in a human carcinoma cell line is compensated not by its paralogue ATF6β but by sustained activation of the IRE1 and PERK arms for tumor growth in nude mice.

ABSTRACT: To survive poor nutritional conditions, tumor cells activate the unfolded protein response, which is composed of the IRE1, PERK, and ATF6 arms, to maintain the homeostasis of the endoplasmic reticulum, where secretory and transmembrane proteins destined for the secretory pathway gain their correct three-dimensional structure. The requirement of the IRE1 and PERK arms for tumor growth in nude mice is established. Here we investigated the requirement for the ATF6 arm, which consists of ubiquitously expressed ATF6α and ATF6β, by constructing ATF6α-knockout (KO), ATF6β-KO, and ATF6α/β-double KO (DKO) in HCT116 cells derived from human colorectal carcinoma. Results showed that these KO cells grew similarly to wild-type (WT) cells in nude mice, contrary to expectations from our analysis of ATF6α

SUBMITTER: Jin S 

PROVIDER: S-EPMC10011727 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature