Loss of STIM2, but not of STIM1, drives colorectal cancer metastasis through metabolic reprogramming and the ATF4 ER stress pathway.

ABSTRACT: The large amounts of calcium (Ca²⁺) stored in the endoplasmic reticulum (ER) and the controlled release of this Ca²⁺ store into the cytosol regulate many cellular functions, and altered ER Ca²⁺ homeostasis induces ER stress. Stromal-interacting molecules 1 and 2 (STIM1/2) are homologous ER-resident Ca²⁺ sensors that synergistically activate cytosolic Ca²⁺ influx through Orai channels to promote Ca²⁺-dependent changes in gene expression and ER Ca²⁺ refilling. Here, we demonstrated that reduced abundance of STIM2, but not that of STIM1, was associated with poor prognosis in colorectal cancer (CRC). STIM2-deficient CRC cells showed enhanced ER Ca²⁺ content in a manner dependent on the ER Ca²⁺ pu

SUBMITTER: Pathak T 

PROVIDER: S-EPMC12507093 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature