Mitochondria as the main drivers of metabolic symbiosis within cancer microenvironment embryogenesis”
Dept. of Experimental and Clinical Biomedical Sciences, Human Health Medical School, University of Florence, Italy
Host: Dr. Giovanna Grimaldi
Tel. 081/6132578; e-mail: firstname.lastname@example.org
Metabolic reprogramming as well as the flexible utilisation of fuel sources by tumour cells has been considered not only intrinsic to malignant cells but also sustained by resident and/or recruited stromal cells. The complexity of tumour-stroma cross-talk is experienced by neoplastic cells through profound changes in the own metabolic machinery. Cancer-associated fibroblasts (CAFs) are the major cellular stromal component of many solid tumors. CAFs establish a metabolic symbiosis with cancer cells, contributing to cancer aggressiveness through lactate shuttle. In such context, mitochondria are dynamic organelles that receive, orchestrate and exchange a multiplicity of stromal cues within the tumour cells to finely regulate key metabolic and signalling pathways, allowing malignant cells to adapt and thrive in an ever-changing environment. Lactate uptake alters the NAD+/NADH ratio in the cancer cells, which culminates with SIRT1-dependent PGC-1α activation and subsequent enhancement of mitochondrial mass and activity. The high exploitation of mitochondria results in tricarboxylic acid cycle deregulation, accumulation of oncometabolites and in the altered expression of mitochondrial complexes, responsible for superoxide generation. Additionally, cancer cells hijack CAF-derived functional mitochondria through the formation of cellular bridges, a phenomenon that we observed in both in vitro and in vivo prostate cancer models. Our results reveal a crucial function of tumor mitochondria as the energy sensors and transducers of CAF-dependent metabolic reprogramming and underscores the reliance of cancer cells on CAF catabolic activity and mitochondria trading.