Tumor Cells and Cancer-Associated Fibroblasts: An Updated Metabolic Perspective.

Abstract

Simple SummaryTumors are a complex ecosystem including not only cancer cells, but also many distinct cell types of the tumor micro-environment. While the Warburg effect assessing high glucose uptake in tumors was recognized a long time ago, metabolic heterogeneity within tumors has only recently been demonstrated. Indeed, several recent studies have highlighted other sources of carbon than glucose, including amino acids, fatty acids and lactate. These newly identified metabolic trajectories modulate key cancer cell features, such as invasion capacities. In addition, cancer metabolic heterogeneity is not restricted to cancer cells. Here, we also describe heterogeneity of Cancer-Associated Fibroblast (CAF) subpopulations and their complex metabolic crosstalk with cancer cells.During the past decades, metabolism and redox imbalance have gained considerable attention in the cancer field. In addition to the well-known Warburg effect occurring in tumor cells, numerous other metabolic deregulations have now been reported. Indeed, metabolic reprograming in cancer is much more heterogeneous than initially thought. In particular, a high diversity of carbon sources used by tumor cells has now been shown to contribute to this metabolic heterogeneity in cancer. Moreover, the molecular mechanisms newly highlighted are multiple and shed light on novel actors. Furthermore, the impact of this metabolic heterogeneity on tumor microenvironment has also been an intense subject of research recently. Here, we will describe the new metabolic pathways newly uncovered in tumor cells. We will also have a particular focus on Cancer-Associated Fibroblasts (CAF), whose identity, function and metabolism have been recently under profound investigation. In that sense, we will discuss about the metabolic crosstalk between tumor cells and CAF.