Metabolic reprogramming of carcinoma-associated fibroblasts and its impact on metabolic heterogeneity of tumors.
Tumor metabolism is characterized with up-regulated glucose uptake and glycolytic rate of tumor cells as the source of ATP and tumors growth, and regulated by a poorly defined combination of cell-intrinsic and extrinsic factors. Metabolic heterogeneity of human tumors is dependent upon the mutational status of specific oncogenes and influenced by tumor microenvironment. Carcinoma-associated fibroblasts (CAFs) adapt in a dynamic manner to the metabolic needs of cancer cells, associated with tumorigenesis and resistance to treatments. Importantly, CAFs could directly "feed" cancer cells essential nutrients and energy-rich metabolites, including lactate, ketone bodies, fatty acids, glutamine, and other amino acids through the induction of autophagy in a host-parasite pattern, to contribute to tumor growth and metastasis. To define the reciprocal metabolic interplay between CAFs and cancer cells will provide a better understanding of molecular mechanisms by which the treatment resistance occurs,and aid in the rational design of metabolism-based approaches to enhance the efficacy of immunotherapy.
Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Institute of Clinical Bioinformatics, Shanghai, China.
Duojiao
D
Wu
Wenzhou Medical University, Wenzhou, China.
Leying
L
Zhuo
Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Institute of Clinical Bioinformatics, Shanghai, China. Electronic address: xiangdong.wang@clintransmed.org.
Xiangdong
X
Wang
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D000596:Amino Acids
Carcinoma-associated fibroblast; Metabolic heterogeneity; Metabolic reprogramming; Tumor