Metabolic reprogramming and epithelial‐to‐mesenchymal transition in cancer

Abstract

Several lines of evidence indicate that during transformation epithelial cancer cells can acquire mesenchymal features via a process called epithelialto-mesenchymal transition (EMT). This process endows cancer cells with increased invasive and migratory capacity, enabling tumour dissemination and metastasis. EMT is associated with a complex metabolic reprogramming, orchestrated by EMT transcription factors, which support the energy requirements of increased motility and growth in harsh environmental conditions. The discovery that mutations in metabolic genes such as FH, SDH and IDH activate EMT provided further evidence that EMT and metabolism are intertwined. In this review, we discuss the role of EMT in cancer and the underpinning metabolic reprogramming. We also put forward the hypothesis that, by altering chromatin structure and function, metabolic pathways engaged by EMT are necessary for its full activation.

FRK plays an oncogenic role in non‐small cell lung cancer by enhancing the stemness phenotype via induction of metabolic reprogramming

“…39 EMT is also associated closely with metabolic reprogramming via its transcription factors and supports the energy requirement for increased motility and growth in the tumor microenvironment. 40 Consistent with previous results, our research also indicated an increase in E-cadherin and inhibition of Twist and Vimentin upon FRK absence, in parallel with damage to stemness and induction of metabolic reprogramming. Given such results, we reasoned that the interaction of the metabolic reprogramming and EMT maintained the stemness in lung cancer, which causes resistance to conventional treatment.…”

“…Tumor cells can acquire CSC‐like properties through the EMT process, which is mediated by important transcription factors including Snail 1/2, Twist 1/2, E‐cadherin and Vimentin . EMT is also associated closely with metabolic reprogramming via its transcription factors and supports the energy requirement for increased motility and growth in the tumor microenvironment . Consistent with previous results, our research also indicated an increase in E‐cadherin and inhibition of Twist and Vimentin upon FRK absence, in parallel with damage to stemness and induction of metabolic reprogramming.…”

LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer

“…In line with the above mentioned findings, our results also demonstrate that during colonization of the brain these features seem even more important than migration and invasion. It is well accepted that, besides migration and invasion, EMT is associated with a complex metabolic reprogramming and chemotherapy resistance . Unfortunately, the previous observations failed to distinguish between the impact of EMT‐induced migration and invasion and the impact of the EMT‐associated metabolic reprogramming.…”

Spleen tyrosine kinase SYK(L) interacts with YY1 and coordinately suppresses SNAI2 transcription in lung cancer cells

“…In the initiation of metastasis, an early step of invasion is largely mediated by the reversible epithelial‐to‐mesenchymal transition (EMT) process, which is associated with the increased resistance to conventional clinical therapies . The EMT process is largely regulated by several transcription factors such as those of the TWIST, the SNAIL, and the ZEB family . Although the exact mechanisms are not well understood, the process of EMT regulation seems to be involved in the cell adhesion and migration during cancer progression, with opportunities for metastasis control.…”