Cancer Metabolism and Metastasis

Metabolic abnormalities are a major feature of cancer, such as increased substance anabolic pathways and aerobic glycolysis. Cancer metabolism shows flexibility and plasticity, which are crucial for the survival and growth of cancer cells. Cancer metastasis is completed in five steps i.e. invasion, dissemination, circulating tumor cells, colonization, and secondary tumor formation. Recently, metabolic adaptation mechanism of cancer metastasis has been proposed to reveal the extensive relationship between cancer metabolism and cancer metastasis. Metastasizing cancer cells selectively and dynamically adapt their metabolism during the complex multistep cascade.

Many nutrients can promote metabolite plasticity during metastasis. For example, lactic acid and pyruvate are the nutrients that cells can directly absorb from the environment; many cancer cells take up glutamine, which contributes to non-essential amino acid as well as nucleotide synthesis through nitrogen or carbon metabolism. Inhibiting the function of key enzymes in metabolic pathways can in turn inhibit the proliferation of cancer cells. For example, lactate dehydrogenase A or B (LDH-A or -B) knockdown can inhibit breast cancer cell motility in vitro. Oncogenic signaling pathways, such as Myc, phosphoinositide 3-kinase (PI3K)/AKT pathway, MAPK/ERK pathway, LKB1/AMPK pathway and Hippo pathways, mediate metabolic gene expression and increase metabolic enzyme activities.