Microenvironmental stress drives tumor cell maladaptation and malignancy through regulation of mitochondrial and nuclear cytochrome c oxidase subunits

Abstract

How microenvironmental stress (hypoxia, acidity, and high glucose) supports tumor growth has not yet been fully elucidated. Here, we demonstrated that these stressors promote malignancy by controlling the expression of cytochrome c oxidase I (COX I), and COX IV-1 and COX IV-2 based on the “energy phenotype” of cancer cells (OXPHOS vs. fermentation). Our results uncover a novel process by which the “energy phenotype” of cancer cells drives the adaptive response to microenvironment stress.