Loss of STIM2 in colorectal cancer drives growth and metastasis through metabolic reprogramming and PERK-ATF4 endoplasmic reticulum stress pathway.

ABSTRACT: The endoplasmic reticulum (ER) stores large amounts of calcium (Ca²⁺), and the controlled release of ER Ca²⁺ regulates a myriad of cellular functions. Although altered ER Ca²⁺ homeostasis is known to induce ER stress, the mechanisms by which ER Ca²⁺ imbalance activate ER stress pathways are poorly understood. Stromal-interacting molecules STIM1 and STIM2 are two structurally homologous ER-resident Ca²⁺ sensors that synergistically regulate Ca²⁺ influx into the cytosol through Orai Ca²⁺ channels for subsequent signaling to transcription and ER Ca²⁺ refilling. Here, we demonstrate that reduced STIM2, but not STIM1, in colorectal cancer (CRC) is associated with poor patient prognosis. Loss of STIM2 causes

SUBMITTER: Pathak T 

PROVIDER: S-EPMC10592933 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature