Role of Metabolic Reprogramming in Epithelial⁻Mesenchymal Transition (EMT).

Hyunkoo Kang,BuHyun Youn,Hyunwoo Kim,HyeSook Youn,Sungmin Lee

doi:10.3390/ijms20082042

Abstract

Activation of epithelial–mesenchymal transition (EMT) is thought to be an essential step for cancer metastasis. Tumor cells undergo EMT in response to a diverse range of extra- and intracellular stimulants. Recently, it was reported that metabolic shifts control EMT progression and induce tumor aggressiveness. In this review, we summarize the involvement of altered glucose, lipid, and amino acid metabolic enzyme expression and the underlying molecular mechanisms in EMT induction in tumor cells. Moreover, we propose that metabolic regulation through gene-specific or pharmacological inhibition may suppress EMT and this treatment strategy may be applied to prevent tumor progression and improve anti-tumor therapeutic efficacy. This review presents evidence for the importance of metabolic changes in tumor progression and emphasizes the need for further studies to better understand tumor metabolism.

Highlights

It is widely accepted that tumorigenesis is initiated by gain-of-function of oncogenic genes and loss-of-function of tumor suppressor genes in normal cells, which as a result, show loss of normal function and uncontrolled proliferation [1]
The mutation in tumor suppressive genes are more significantly involved in tumorigenesis and Tumor protein p53 (TP53), Breast cancer type 1/2 susceptibility protein (BRCA1/2), and Phosphatase and tensin homolog (PTEN) which protect DNA from mutation accumulation have been suggested as frequently mutated tumor suppressor genes in tumor cells [2]
The upregulation of mitochondrial topoisomerase I (TOP1MT), observed in invasive cancer cells, increases both in vitro and in vivo expression of lactate dehydrogenase A (LDHA), which is associated with enhanced glycolysis and epithelial–mesenchymal transition (EMT) in gastric cancer cells [56]

Summary

Introduction

It is widely accepted that tumorigenesis is initiated by gain-of-function of oncogenic genes and loss-of-function of tumor suppressor genes in normal cells, which as a result, show loss of normal function and uncontrolled proliferation [1]. The mutation in tumor suppressive genes are more significantly involved in tumorigenesis and Tumor protein p53 (TP53), Breast cancer type 1/2 susceptibility protein (BRCA1/2), and Phosphatase and tensin homolog (PTEN) which protect DNA from mutation accumulation have been suggested as frequently mutated tumor suppressor genes in tumor cells [2]. It has been suggested that altered metabolism increases the vulnerability of cancer cells to mutagenesis and epigenetic alteration [13,14] These studies suggest that somatic mutations, epigenetic alterations, and metabolic reprogramming form a feed-forward cycle that leads to tumor malignancy. We discuss the clinical potential of metabolic enzyme-specific inhibitors for the suppression of tumor metastasis

Glucose Metabolism in EMT

Lipid Metabolism in EMT

Amino Acid Metabolism in EMT

Clinical Significance of Metabolic Regulation in Cancer Therapy

Findings

Conclusions