학술논문

Stochastic epithelial-mesenchymal transitions diversify non-cancerous lung cell behaviours.
Document Type
Academic Journal
Author
Bhatia S; Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba 4102, QLD, Australia. Electronic address: s3.bhatia@qut.edu.au.; Gunter JH; Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba 4102, QLD, Australia; Australian Prostate Cancer Research Centre-Queensland (APCRC-Q), Queensland University of Technology, Woolloongabba 4102, Australia.; Burgess JT; Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba 4102, QLD, Australia.; Adams MN; Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba 4102, QLD, Australia.; O'Byrne K; Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba 4102, QLD, Australia; Princess Alexandra Hospital, Woolloongabba 4102, QLD, Australia.; Thompson EW; Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba 4102, QLD, Australia.; Duijf PH; Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba 4102, QLD, Australia; Centre for Cancer Biology, Clinical and Health Sciences, University of South Australia and SA Pathology, Adelaide SA, 5001, Australia; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. Electronic address: pascal.duijf@unisa.edu.au.
Source
Publisher: Neoplasia Press Country of Publication: United States NLM ID: 101472619 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1936-5233 (Print) Linking ISSN: 19365233 NLM ISO Abbreviation: Transl Oncol Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1936-5233
Abstract
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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Inc.)