Metabolic rewiring in the promotion of cancer metastasis: mechanisms and therapeutic implications

Tumor metastasis is the major cause of mortality from cancer. Metabolic rewiring and the metastatic cascade are highly intertwined, co-operating to promote multiple steps of cancer metastasis. Metabolites generated by cancer cells influence the metastatic cascade, encompassing epithelial-mesenchymal...

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Bibliographic Details
Published in:Oncogene 2020-09, Vol.39 (39), p.6139-6156
Main Authors: Wei, Qinyao, Qian, Yun, Yu, Jun, Wong, Chi Chun
Format: Article
Language:English
Subjects:
631/67/2327
631/67/322
Amino acids
Apoptosis
Cancer
Cell Biology
Colonization
Enzymes
Epigenetic inheritance
Epigenetics
Health aspects
Human Genetics
Humans
Internal Medicine
Matrix metalloproteinase
Medicine
Medicine & Public Health
Mesenchyme
Metabolism
Metabolites
Metastases
Metastasis
Molecular modelling
Neoplasm Metastasis - immunology
Neoplasms - complications
Neoplasms - pathology
Oncology
Oxidative stress
Physiological aspects
Review
Review Article
Stem cells
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Summary:Tumor metastasis is the major cause of mortality from cancer. Metabolic rewiring and the metastatic cascade are highly intertwined, co-operating to promote multiple steps of cancer metastasis. Metabolites generated by cancer cells influence the metastatic cascade, encompassing epithelial-mesenchymal transition (EMT), survival of cancer cells in circulation, and metastatic colonization at distant sites. A variety of molecular mechanisms underlie the prometastatic effect of tumor-derived metabolites, such as epigenetic deregulation, induction of matrix metalloproteinases (MMPs), promotion of cancer stemness, and alleviation of oxidative stress. Conversely, metastatic signaling regulates expression and activity of rate-limiting metabolic enzymes to generate prometastatic metabolites thereby reinforcing the metastasis cascade. Understanding the complex interplay between metabolism and metastasis could unravel novel molecular targets, whose intervention could lead to improvements in the treatment of cancer. In this review, we summarized the recent discoveries involving metabolism and tumor metastasis, and emphasized the promising molecular targets, with an update on the development of small molecule or biologic inhibitors against these aberrant situations in cancer.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-020-01432-7