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.

LncRNA HOXA‐AS3 promotes the malignancy of glioblastoma through regulating miR‐455‐5p/USP3 axis

“…Epithelial-mesenchymal transition is a process in which epithelial cells are transformed into mesenchymal cells and acquire motile and invasive characteristics. 27,28 Recent studies have proven that USP3 promotes GBM progress by regulating the EMT process. 18,29 Therefore, in order to study the molecular mechanism of lncRNA HOXA-AS3 promoting GBM transfer, we detected the level of EMT-related biomarkers in GBM cells F I G U R E 6 MiR-455-5p rescued effect on the proliferation and invasion of lncRNA HOXA-AS3 overexpression glioblastoma multiforme (GBM) cells.…”

Identification and Validation of a Five-gene Signature Associated with Overall Survival in Breast Cancer Patients

“…The EMT represented a biological process during which polarized epithelial cells lost cell identity and experienced various biochemical alterations that allowed it to assume mesenchymal phenotypes [26]. Normally observed during embryonic development, EMT could also be involved in various pathological conditions.…”

“…Normally observed during embryonic development, EMT could also be involved in various pathological conditions. Once hijacked by cancer cells, EMT often led to enhanced migration capability, acquisition of resistance to apoptosis, and increased cell proliferation [26][27][28][29]. Thus, we examined the role of selected genes in EMT signaling pathway in breast cancer cells.…”

Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic

“…Epithelial-to-mesenchymal transition (EMT) represents a biological program during which epithelial cells lose their identity and acquire a mesenchymal phenotype [ 15 ]. Thus, EMT has dual biological roles, playing a physiological role in sustaining organismal development, but under pathological conditions such as cancer, EMT is associated with increased invasion and migration rates that further promote high metastatic rates [ 15 , 16 ]. This process can be snatched by cancer cells, being frequently linked with resistance to apoptosis, acquisition of cancer stem cell characteristics, and drug resistance [ 16 ].…”

“…Thus, EMT has dual biological roles, playing a physiological role in sustaining organismal development, but under pathological conditions such as cancer, EMT is associated with increased invasion and migration rates that further promote high metastatic rates [ 15 , 16 ]. This process can be snatched by cancer cells, being frequently linked with resistance to apoptosis, acquisition of cancer stem cell characteristics, and drug resistance [ 16 ]. EMT programs/processes/mechanisms promote CSC stemness in many epithelial tissues; therefore, understanding these relationships may highlight different therapeutic vulnerabilities that can be further exploited in clinical practice [ 17 ].…”