Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

被引:65
|
作者
Sinha, Dona [1 ]
Saha, Priyanka [1 ]
Samanta, Anurima [1 ]
Bishayee, Anupam [2 ]
机构
[1] Chittaranjan Natl Canc Inst, Dept Receptor Biol & Tumour Metastasis, Kolkata 700026, India
[2] Lake Erie Coll Osteopath Med, Bradenton, FL 34211 USA
关键词
collective migration; epithelial/mesenchymal phenotype; phenotypic stability factor; hybrid/partial EMT; metastasis; stemness; CIRCULATING TUMOR-CELLS; NEGATIVE FEEDBACK LOOP; PROSTATE-CANCER; PARTIAL EMT; PLASTICITY; IDENTIFICATION; METASTASIS; EXPRESSION; RESISTANCE; INHIBITORS;
D O I
10.3390/biom10111561
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epithelial mesenchymal transition (EMT) is a complex process through which epithelial (E) cells lose their adherens junctions, transform into mesenchymal (M) cells and attain motility, leading to metastasis at distant organs. Nowadays, the concept of EMT has shifted from a binary phase of interconversion of pure E to M cells and vice versa to a spectrum of E/M transition states preferably coined as hybrid/partial/intermediate EMT. Hybrid EMT, being a plastic transient state, harbours cells which co-express both E and M markers and exhibit high tumourigenic properties, leading to stemness, metastasis, and therapy resistance. Several preclinical and clinical studies provided the evidence of co-existence of E/M phenotypes. Regulators including transcription factors, epigenetic regulators and phenotypic stability factors (PSFs) help in maintaining the hybrid state. Computational and bioinformatics approaches may be excellent for identifying new factors or combinations of regulatory elements that govern the different EMT transition states. Therapeutic intervention against hybrid E/M cells, though few, may evolve as a rational strategy against metastasis and drug resistance. This review has attempted to present the recent advancements on the concept and regulation of the process of hybrid EMT which generates hybrid E/M phenotypes, evidence of intermediate EMT in both preclinical and clinical setup, impact of partial EMT on promoting tumourigenesis, and future strategies which might be adapted to tackle this phenomenon.
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页码:1 / 22
页数:22
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