Overexpression of CD44 Standard Isoform Upregulates HIF-1α Signaling in Hypoxic Breast Cancer Cells

Biomolecules & Therapeutics
Dayoung RyuMi-Kyoung Kwak

Abstract

Cluster of differentiation 44 (CD44), a cell surface receptor for hyaluronic acid (HA), is involved in aggressive cancer phenotypes. Herein, we investigated the role of the CD44 standard isoform (CD44s) in hypoxia-inducible factor-1α (HIF-1α) regulation using MCF7 overexpressing CD44s (pCD44s-MCF7). When pCD44s-MCF7 was incubated under hypoxia, levels of HIF-1α, vascular endothelial growth factor, and the HIF-1α response element-derived luciferase activity were significantly increased compared to those in the control MCF7. Incubation of pCD44s-MCF7 cells with HA further increased HIF-1α accumulation, and the silencing of CD44s attenuated HIF-1α elevation, which verifies the role of CD44s in HIF-1α regulation. In addition, the levels of phosphorylated extracellular signal-regulated kinase (ERK) was higher in hypoxic pCD44s-MCF7 cells, and HIF-1α accumulation was diminished by the pharmacological inhibitors of ERK. CD44s-mediated HIF-1α augmentation resulted in two functional outcomes. First, pCD44s-MCF7 cells showed facilitated cell motility under hypoxia via the upregulation of proteins associated with epithelialmesenchymal transition, such as SNAIL1 and ZEB1. Second, pCD44s-MCF7 cells exhibited higher levels of glycolytic prot...Continue Reading

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Citations

Apr 12, 2019·International Journal of Molecular Sciences·Peter KubatkaDietrich Büsselberg
May 23, 2019·Current Opinion in Clinical Nutrition and Metabolic Care·Andrew RedfernErik W Thompson
Aug 25, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Li ChenQuan Wei
Dec 19, 2020·Frontiers in Oncology·Antons MartincuksLorna Rodriguez-Rodriguez
Nov 21, 2021·Experimental Hematology & Oncology·Jun ZhangLiming Chen

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Methods Mentioned

BETA
transfection
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GraphPad Prism

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