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  • HIF-1a regulates hypoxia-induced autophagy via translocation of ANKRD37 in colon cancer.

HIF-1a regulates hypoxia-induced autophagy via translocation of ANKRD37 in colon cancer.

Experimental cell research (2020-07-18)
Minzi Deng, Weizhi Zhang, Lingling Yuan, Jieqiong Tan, Zhihong Chen
ABSTRACT

Autophagy is a basic catabolic response that eukaryotic cells use to degrade unnecessary or dysfunctional cellular components in an orderly and regulated manner. It plays important roles in maintaining cellular homeostasis, energy homeostasis, response to environmental stimuli, and the development of cancer. In solid tumors, hypoxia induces an increased HIF-1a that activates autophagy. However, the exact mechanism by which induced HIF-1a stimulates autophagy in cancer cells remains elusive. In the present study, we confirmed that ANKRD37 is upregulated in colon cancer tissue. Moreover, the higher expression level of ANKRD37 is related to a poorer survival rate. Using RNA interference, immunoblot, and immunofluorescence, we discovered that in cancer cell line RKO, hypoxia-induced HIF-1a regulates autophagy activity by increasing ANKRD37 level. In addition, intranuclear ANKRD37 played an important role in the regulation of hypoxia-induced autophagy. The translocation of ANKRD37 into cell nuclear is required for promoting cell growth and HIF-1a induced autophagy. These findings provide new insights to understand the hypoxia regulation mechanisms and the role of autophagy in cancer development.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Bovine Serum Albumin, chromatographically purified, New Zealand origin, low endotoxin, suitable for cell culture, pH 7, ≥98%
Sigma-Aldrich
Paraformaldehyde, reagent grade, crystalline
Sigma-Aldrich
Phosphate buffered saline, 10× concentrate, BioPerformance Certified, suitable for cell culture
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Phosphate Buffered Saline with 0.05% TWEEN® 20, pH 7.4