Epithelial Mesenchymal Transition (EMT) and Associated Invasive Adhesions in Solid and Haematological Tumours

Abstract

In solid tumours, cancer cells that undergo epithelial mesenchymal transition (EMT) express characteristic gene expression signatures that promote invasive migration as well as the development of stemness, immunosuppression and drug/radiotherapy resistance, contributing to the formation of currently untreatable metastatic tumours. The cancer traits associated with EMT can be controlled by the signalling nodes at characteristic adhesion sites (focal contacts, invadopodia and microtentacles) where the regulation of cell migration, cell cycle progression and pro-survival signalling converge. In haematological tumours, ample evidence accumulated during the last decade indicates that the development of an EMT-like phenotype is indicative of poor disease prognosis. However, this EMT phenotype has not been directly linked to the assembly of specific forms of adhesions. In the current review we discuss the role of EMT in haematological malignancies and examine its possible link with the progression towards more invasive and aggressive forms of these tumours. We also review the known types of adhesions formed by haematological malignancies and speculate on their possible connection with the EMT phenotype. We postulate that understanding the architecture and regulation of EMT-related adhesions will lead to the discovery of new therapeutic interventions to overcome disease progression and resistance to therapies.

Clinical applications of circulating tumor cells in hepatocellular carcinoma

“…EMT is a complex process involving multiple signaling pathways and transcription factor regulation, the up-regulation of mesenchymal genes and suppression of epithelial genes lead to the transformation of cell morphology and acquisition of stronger invasive migration capability ( 66 ). Many changes in cellular shape and vitality, such as loss of cellular polarity, the disappearance of intercellular adhesion, and the acquisition of enhanced motility, which promote cells to fall off from tumor tissues and invade into blood vessels ( 64 , 67 , 68 ). EMT process facilitates the secretion of matrix metalloproteinase (MMP), which degrades the extracellular matrix to cause cell migration, tissue invasion and blood vessel infiltration ( 69 ).…”

“…EMT is believed to play an important role in tumor occurrence and progression. The studies have demonstrated that the expression of EMT markers is associated with an aggressive malignant phenotype and with poor prognosis in cancer patients ( 65 , 67 , 70 ).…”

“…EMT promotes the spread of cancer cells from the primary tumor into the blood. Upon arrival at a suitable secondary location, CTCs undergo the MET transformation from the non-proliferative or low-proliferative migratory phenotype to a proliferative type, resulting in distant metastasis ( 64 , 67 , 76 ). To form micro-metastases or develop into metastatic cancers, CTCs are considered to have a corresponding colonization ability in the blood circulation ( 77 , 78 ).…”

The Role of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease

“…However, EndoMT recurs postnatally during the development of various cardiovascular diseases (CVDs), such as atherosclerosis, adult valve diseases, myocardial fibrosis, and pulmonary arterial hypertension (PAH) [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. In the EndoMT transitional process, endothelial cells progressively lose endothelial-specific markers and gain mesenchymal phenotypes [ 45 ]. The expression of cell–cell adhesion proteins is downregulated, but mesenchyme-specific factors are increased [ 46 ].…”

CNTN-1 Upregulation Induced by Low-Dose Cisplatin Promotes Malignant Progression of Lung Adenocarcinoma Cells via Activation of Epithelial-Mesenchymal Transition

“…Epithelial-mesenchymal transition (EMT) is a dynamic cellular reprogramming process through which epithelial cells undergo morphological changes characterized by loss of cell-cell adhesion and acquisition of mobile fibroblast-like phenotype. A previous study demonstrated that EMT progression participated in embryonic development and tissue remolding ( Greaves and Calle, 2022 ). Subsequent evidence suggested that the aberrant activation of the EMT process promoted metastasis, invasion, and drug resistance of multiple epithelial carcinomas, such as gastric carcinoma, breast cancer, and lung cancer ( Menju and Date, 2021 ; Azimi et al, 2022 ; Buyuk et al, 2022 ).…”