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

Figure 6

Overexpressed GDF15 displayed high correlation with CHOP in human CRC. (a-b) Representative images of IHC staining of GDF15 protein (a) and CHOP protein (b) in paired peritumor and tumor tissue slides from human CRC patients (n = 21 patients). Scale bar, 50 μm. Results of quantitative integrated optical density (IOD) analysis were shown, respectively. value is noted in the figure by unpaired two-tailed Student’s t-test. (c-d) Linear regression analysis of mRNA levels of indicated genes in tumors of CRC patients. The coefficient of determination (r²) and value are indicated. (e) Schematic model of this study. In colorectal carcinoma, hypoxic exposure causes ER stress and triggers the activation of UPR signaling pathway, including PERK-eIF2α branch. Elevated CHOP binds to the promoter and activates the expression of GDF15, which increases the levels of intracellular fatty acids β-oxidation. GDF15 promotes the metastasis as well as the growth of CRC cells.

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