Hypoxia Induces Growth Differentiation Factor 15 to Promote the Metastasis of Colorectal Cancer via PERK-eIF2α Signaling.

ABSTRACT: Hypoxia plays an essential role in orchestrating Epithelial-mesenchymal transition and promoting metastasis of colorectal cancer. However, the underlying mechanisms are still not well elucidated. Here, we present that hypoxic exposure causes endoplasmic reticulum stress and activates the unfolded protein response pathways, which drives GDF15 expression in colorectal cancer cells. Mechanistically, upregulated CHOP led by activated PERK-eIF2α signaling promotes GDF15 transcription via directly binding to its promoter. Further study implicates that hypoxia-induced GDF15 is required for the EMT and invasion of colorectal cancer cells; enforced expression of GDF15 promotes the mitochondrial oxidation of fatty acids in colorectal cancer cells. Moreover, the abrogation of GDF15 results in

SUBMITTER: Zheng H 

PROVIDER: S-EPMC7008299 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature