Linking Metabolic Reprogramming, Plasticity and Tumor Progression

Abstract

The specific molecular features of cancer cells that distinguish them from the normal ones are denoted as “hallmarks of cancer”. One of the critical hallmarks of cancer is an altered metabolism which provides tumor cells with energy and structural resources necessary for rapid proliferation. The key feature of a cancer-reprogrammed metabolism is its plasticity, allowing cancer cells to better adapt to various conditions and to oppose different therapies. Furthermore, the alterations of metabolic pathways in malignant cells are heterogeneous and are defined by several factors including the tissue of origin, driving mutations, and microenvironment. In the present review, we discuss the key features of metabolic reprogramming and plasticity associated with different stages of tumor, from primary tumors to metastases. We also provide evidence of the successful usage of metabolic drugs in anticancer therapy. Finally, we highlight new promising targets for the development of new metabolic drugs.

p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells

“…In general, malignant cells have 1.5-2 times higher MMP levels than their non-malignant counterparts, which is the consequence of an elevated energy metabolism. The level of MMP enhancement is associated with the degree of malignancy of neoplastic cells, including enhanced resistance to aggressive conditions and elevation of their metastatic potential (28).…”

“…c-Myc and HIF1A are master regulators of metabolic networks. They upregulate and coordinate glycolysis, respiration, one-carbon metabolism, and the metabolism of glutamine and lipids upon tumorigenesis (28,40,41). It is important to note that HIF1A and c-Myc are both known to regulate the expression of tumor-specific isoforms of glycolytic proteins such as GLUT1, HK2, PKM, and LDHA, thereby diminishing the Warburg effect in cancer cells (42)(43)(44).…”

Epithelial–Mesenchymal Transition (EMT) Induced by TGF-β in Hepatocellular Carcinoma Cells Reprograms Lipid Metabolism

“…However, notably, the expression of the lipogenic enzymes FASN and ACC are down-regulated in circulating breast cancer cells, which exhibit enhanced mitochondrial respiration that fuels cancer cell motility [ 20 ]. EMT cells undergo oxidative shock upon intravasation of blood cells, followed by attacks from the immune system and requirement of anchorage-independent survival [ 21 ]. Switching their glycolytic metabolism towards a hybrid, more oxidative state would allow them to adapt to the environment, whereupon they find a new metastatic niche [ 22 ].…”

Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI

“…Another possible contributor to this lower acidification of the TME could be a compensatory mechanism occurring when tumors are treated chronically with an MPC inhibitor. Tumor cells indeed exhibit extraordinary metabolic plasticity to adapt to constraints or changes in their environment [ 6 , 43 , 44 , 45 , 46 ]. It has been previously demonstrated that cells may tolerate loss of MPC activity by metabolic rewiring to compensate for the loss of pyruvate oxidation [ 8 ].…”