Heterogeneity and plasticity of epithelial–mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms

Abstract

Epithelial–mesenchymal transition (EMT) or mesenchymal–epithelial transition (MET) plays critical roles in cancer metastasis. Recent studies, especially those based on single‐cell sequencing, have revealed that EMT is not a binary process, but a heterogeneous and dynamic disposition with intermediary or partial EMT states. Multiple double‐negative feedback loops involved by EMT‐related transcription factors (EMT‐TFs) have been identified. These feedback loops between EMT drivers and MET drivers finely regulate the EMT transition state of the cell. In this review, the general characteristics, biomarkers and molecular mechanisms of different EMT transition states were summarized. We additionally discussed the direct and indirect roles of EMT transition state in tumour metastasis. More importantly, this article provides direct evidence that the heterogeneity of EMT is closely related to the poor prognosis in gastric cancer. Notably, a seesaw model was proposed to explain how tumour cells regulate themselves to remain in specific EMT transition states, including epithelial state, hybrid/intermediate state and mesenchymal state. Additionally, this article also provides a review of the current status, limitations and future perspectives of EMT signalling in clinical applications.

Pirfenidone inhibits TGF‐β1‐induced metabolic reprogramming during epithelial‐mesenchymal transition in non‐small cell lung cancer

“…The main therapeutic target of PFD is TGF‐β1, which is the classical EMT promoter. Studies have found that EMT is closely related to tumour metabolism 32,33 . Our experiments showed that PFD inhibited glycolysis in NSCLC cells.…”

“…TGF‐β1, the main target of PFD, exerts anti‐inflammatory and anti‐fibrotic effects and plays an important role in regulating key glycolytic enzymes 54,55 . TGF‐β1 participates in the crosstalk between EMT and metabolic reprogramming in cancer progression 32,56–58 . The TGF‐β1 signalling pathway is the primary driver of EMT.…”

Acute myeloid leukemia (AML)‐derived mesenchymal stem cells induce chemoresistance and epithelial–mesenchymal transition‐like program in AML through IL‐6/JAK2/STAT3 signaling

“…It had been reported that EMT is dynamic and not a binary process, depending on the cell type and tissue type. Complex aspects orchestrate the EMT, including the pretranscriptional level, transcriptional level, posttranscriptional level, translational level, and posttranslational levels 33,34 . Maybe there were posttranscriptional or posttranslational controls behind the AML‐MSC‐regulated EMT‐like program in AML; this needs to be investigated.…”

Recent Advances and Mechanism of Nanomaterials Promoting Tumor Metastasis

“…Another phenotypic plasticity process associated with metastasis is the epithelial–mesenchymal transition (EMT). Some tumor cells can reduce adhesion and increase invasiveness through EMT, which helps tumor cells detach from the primary site, and then, this part of the tumor cells can grow at a secondary site through the reverse process of mesenchymal–epithelial transition (MET) . The vasculature not only provides nutrients for tumors but also is a way for tumors to metastasize to distant organs.…”

“…Some tumor cells can reduce adhesion and increase invasiveness through EMT, which helps tumor cells detach from the primary site, and then, this part of the tumor cells can grow at a secondary site through the reverse process of mesenchymal−epithelial transition (MET). 11 The vasculature not only provides nutrients for tumors but also is a way for tumors to metastasize to distant organs. The permeability of the vasculature affects the invasion process of the tumor to a large extent.…”