Portal de investigação
Epithelial-Mesenchymal Plasticity Induced by Discontinuous Exposure to TGFß1 Promotes Tumour Growth
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Santos, M
- Ferreira, M
- Oliveira, P
- Mendes, N
- Andre, A
- Vieira, AF
- Nunes, JB
- Carvalho, J
- Rocha, S
- Azevedo, M
- Ferreira, D
- Reis, I
- Vinagre, J
- Heravi Moussavi, A
- Lima, J.
- Burleigh, A
- Roskelley, C
- Huntsman, D
Unidades de investigação
Abstract
Simple Summary In this manuscript, we used a non-genetically manipulated EMT/MET cell line model to demonstrate that epithelial mesenchymal plasticity occurring in normal cells generates co-existing phenotypically and functionally divergent cell subpopulations which result in fast growing tumours in vivo. Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity, favouring tumour growth. We developed an EMT model by on and off exposure of epithelial EpH4 cells (E-cells) to TGF beta 1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia by using RNA sequencing, immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays as well as cell xenografts in nude mice. Phenotypic reverted epithelial cells (RE-cells) obtained after MET induction presented epithelial morphologies and proliferation rates resembling E cells. However, the RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a uniquely heterogeneous mixture of cell subpopulations with a high self-renewal ability. RE cell heterogeneity was stably maintained for long periods after TGF beta 1 removal both in vitro and in large tumours derived from the nude mice. Overall, we show that phenotypic reverted epithelial cells (RE cells) do not return to the molecular and functional epithelial state and present mesenchymal features related to aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cell reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour growth-promoting factor in vivo.
Dados da publicação
- ISSN/ISSNe:
- 2079-7737, 2079-7737
- Tipo:
- Article
- Páginas:
- 1046-
- Link para outro recurso:
- www.scopus.com
BIOLOGY-BASEL Multidisciplinary Digital Publishing Institute (MDPI)
Citações Recebidas na Web of Science: 3
Citações Recebidas na Scopus: 3
Documentos
- Não há documentos
Filiações
Keywords
- MET; cellular heterogeneity; self-Renewal; EMT; tumourigenic potential
Financiamento
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Citar a publicação
Santos M,Ferreira M,Oliveira P,Mendes N,Andre A,Vieira AF,Nunes JB,Carvalho J,Rocha S,Azevedo M,Ferreira D,Reis I,Vinagre J,Paredes J,Heravi A,Lima J,Máximo V,Burleigh A,Roskelley C,Carneiro F,Huntsman D,Oliveira C. Epithelial-Mesenchymal Plasticity Induced by Discontinuous Exposure to TGFß1 Promotes Tumour Growth. Biology-Basel. 2022. 11. (7):p. 1046-1046. IF:4,200. (2).
