Role of hypoxia-inducible factor 1 (HIF1) in tumorigenesis

Abstract

Introduction: Cancer is one of the leading causes of morbidity and mortality worldwide. Proliferation, development and resistance of cancer cells are due to a specific microenvironment in which hypoxia is one of the key components. Purpose: Studying the role of HIF1 in tumorogenesis as well as the mechanisms by which it maintains the supervision of tumor cells to identify new strategies for diagnosis and targeted treatment of cancer. Material and methods: Literature analysis between 2015-2019 through the following search engines PubMed, BMC cancer, AACR publications, Google Scholar, using 12 bibliographic sources. Results:  Rapid and uncontrolled proliferation of tumors limits the availability of O2 and blood, triggering increased expression and stabilization of HIF1α and HIF1β, which in the nucleus induce the expression of glycolytic enzyme: (LDH-A) genes,VEGF gene, EPO, i-NOS and HO-1 genes, the inhibition of BAD and BID (proapoptotic) gene expression.  LDH accumulation converts pyruvate to lactate by providing them with an energy substrate, VEGF induces angiogenesis, and EPO-erythropoiesis, inhibition of BAD and BID gives cells resistance to apoptosis. HIF-1 induces autophagy and inhibits mitochondrial biosynthesis to stop cell death by providing resistance. Conclusions: High levels of HIF 1 in tumor cells can be used as a marker in the early detection of cancer, and inhibition of the factor may stop the development of the tumor.