Fig. 4: Metabolic symbiosis between cancer-associated fibroblasts and HNSCC cells.
From: Cell death in head and neck cancer pathogenesis and treatment
HNSCC cells undergo numerous metabolic changes including increased glutaminolysis. Glutaminolysis produces large pools of intracellular glutamate. Upregulation of the cystine/glutamate antiporter ((Xc–) system) and excitatory amino acid transporter (SLC1A3) promotes aberrant glutamate (Glu) release from cancer cells. Increased stiffness of extracellular matrix during tumour progression induces cancer-associated fibroblasts (CAFs) to import glutamate (through SLC1A3) and release aspartate (Asp) and glutamine (Gln) supporting cancer cell purine/pyrimidine synthesis. Glutamine synthetase (GS) is often overexpressed in these CAFs. CAFs can also promote chemoresistance through the production of glutathione (GSH). Establishing of this metabolic symbiosis is coordinated by a YAP/TAZ-dependent mechanotransduction pathway. Green bubbles indicate activation and pink inhibition of the process.
