Hexose-6-phosphate dehydrogenase controls cancer cell proliferation and migration through pleiotropic effects on the unfolded-protein response, calcium homeostasis, and redox balance

What is it about?

The present study investigated an enzyme called hexose-6-phosphate dehydrogenase (H6PD) and its role in the proliferation and aggressiveness of three different breast cancer cell lines. The H6PD gene is amplified in several types of malignancies, and earlier work pointed towards a potential involvement of the enzyme in cancer cell growth. We show that genetic down regulation of H6PD resulted in reduced proliferation and migratory potential of all three breast cancer cell lines. We investigated the cellular changes following down regulation of H6PD and found altered redox regulation in a subcellular compartment, the endoplasmic reticulum. Many components of an important cellular stress signaling pathway, the unfolded protein response, were affected upon H6PD down regulation. Additionally, cellular calcium homeostasis and energy metabolism were altered upon down regulation of H6PD. These results provide an insight into the mechanisms by which the redox regulation of the endoplasmic reticulum can impact on breast cancer cell properties. Further characterization of the molecular pathways involving H6PD could greatly broaden our understanding of how the endoplasmic reticulum microenvironment sustains malignant cell growth.

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