RhoC modulates metabolic networks in cervical cancer by transcriptionally regulating the expression of genes involved in metabolism

Abstract

ABSTRACTIn their quest for autonomy, tumor cells are known to reroute metabolic networks to aid their proliferation and survival. These metabolic alterations are governed by the tumor sub-population, thereby contributing towards an additional layer of complexity within the already heterogeneous tumor. For instance, bulk proliferative tumor cells rely on completely different pathways for their metabolic requirements as opposed to the stem-like metastatic cells. However, the molecular switch that drives these metabolic changes remains unknown. RhoC is a well-established contributor towards multiple aspects of tumor development including proliferation, EMT, migration, invasion and metastasis. A transcriptomics-based approach on a RhoC overexpressing cervical cancer cell line unveiled distinct metabolic signatures existent in these cells. Oxidative phosphorylation, TCA cycle, nucleic acid metabolism and fatty acid elongation were some of the specific pathways that emerged as up-regulated. This study therefore provides insight into the intricate metabolic circuitry functional in aggressive RhoC-high cells and thus proposes a pivotal role for RhoC in oncometabolism.