Stochastic epithelial-mesenchymal transitions diversify non-cancerous lung cell behaviours

Autor: Sugandha Bhatia, Jennifer H Gunter, Joshua T Burgess, Mark N Adams, Kenneth O'Byrne, Erik W Thompson, Pascal HG Duijf
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Translational Oncology, Vol 37, Iss , Pp 101760- (2023)
Druh dokumentu: article
ISSN: 1936-5233
DOI: 10.1016/j.tranon.2023.101760
Popis: Epithelial-mesenchymal plasticity (EMP) is a hallmark of cancer. By enabling cells to shift between different morphological and functional states, EMP promotes invasion, metastasis and therapy resistance. We report that near-diploid non-cancerous human epithelial lung cells spontaneously shift along the EMP spectrum without genetic changes. Strikingly, more than half of single cell-derived clones adopt a mesenchymal morphology. We independently characterise epithelial-like and mesenchymal-like clones. Mesenchymal clones lose epithelial markers, display larger cell aspect ratios and lower motility, with mostly unaltered proliferation rates. Stemness marker expression and metabolic rewiring diverge independently of phenotypes. In 3D culture, more epithelial clones become mesenchymal-like. Thus, non-cancerous epithelial cells may acquire cancer metastasis-associated features prior to genetic alterations and cancerous transformation.
Databáze: Directory of Open Access Journals