EMT Factors and Metabolic Pathways in Cancer

Abstract

The epithelial-mesenchymal transition (EMT) represents a biological program during which epithelial cells lose their cell identity and acquire a mesenchymal phenotype. EMT is normally observed during organismal development, wound healing and tissue fibrosis. However, this process can be hijacked by cancer cells and is often associated with resistance to apoptosis, acquisition of tissue invasiveness, cancer stem cell characteristics, and cancer treatment resistance. It is becoming evident that EMT is a complex, multifactorial spectrum, often involving episodic, transient or partial events. Multiple factors have been causally implicated in EMT including transcription factors (e.g., SNAIL, TWIST, ZEB), epigenetic modifications, microRNAs (e.g., miR-200 family) and more recently, long non-coding RNAs. However, the relevance of metabolic pathways in EMT is only recently being recognized. Importantly, alterations in key metabolic pathways affect cancer development and progression. In this review, we report the roles of key EMT factors and describe their interactions and interconnectedness. We introduce metabolic pathways that are involved in EMT, including glycolysis, the TCA cycle, lipid and amino acid metabolism, and characterize the relationship between EMT factors and cancer metabolism. Finally, we present therapeutic opportunities involving EMT, with particular focus on cancer metabolic pathways.

Keywords: EMT; cancer metabolism; metabolic pathways; non-coding RNAs; transcription factors.

Figure 1

Interplay of glycolysis pathway with EMT factors. Enzymes are depicted in yellow font, EMT-related factors are depicted in red font. → denotes induction; ⊣ denotes inhibition. Yellow dots indicate intermediate reactions that are not depicted.

Figure 2

Crosstalk of TCA cycle with EMT factors. Enzymes are depicted in yellow font, EMT-related factors are depicted in red font. → denotes induction; ⊣ denotes inhibition.

Figure 3

Fatty acid metabolism and EMT factors. Enzymes are depicted in yellow font, EMT-related factors are depicted in red font. → denotes induction; ⊣ denotes inhibition.

Figure 4

Points of convergence between amino acid metabolism and EMT. Enzymes are depicted in yellow font, EMT-related factors are depicted in red font. → denotes induction.