Abstract: Elevated glycolysis and impaired oxidative phosphorylation (Warburg effect) is one of the classical features of cancer. Cancer cells, in order to support their growth and proliferation needs both high energy and more biosynthetic intermediates, therefore they alter their metabolic activities. However, high proliferation rate of tumor cells often generates regions that become oxygen deficient. Therefore, their carbohydrate metabolism depends mostly on a glycolytic process that is coupled with oxidative phosphorylation. This metabolic switch, also known as the Warburg Effect, constitutes a fundamental adaptation of the tumor cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. The glycolyic phenotype created due to Warburg Effect grants the cancer cells, in hypoxic conditions; a growth advantage by inducing various pro-proliferative and pro-invasive process like angiogenesis. This, tumor glycolysis may constitute an attractive target for cancer therapy. In this review, we discuss some of the mechanisms by which cancer cell metabolism may shape and modify the tumor microenvironment. Also, we will detail how two specific environmental factors present in the tumor microenvironment including hypoxia and acidosis, reciprocally affect cancer cell metabolism.
Keywords: Tumor microenvironment, Glutaminolysis, Chronic acidosis, Tumor hypoxia