Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/193843
Title: | 3D collagen migration patterns reveal a SMAD3-dependent and TGF-β1-independent mechanism of recruitment for tumour-associated fibroblasts in lung adenocarcinoma |
Author: | Juste Lanas, Yago Díaz Valdivia, Natalia Llorente, Alejandro Ikemori, Rafael Bernardo, Alejandro Arshakyan, Marselina Borau, Carlos Ramírez Ruz, J. (José) Ruffinelli, José Carlos Nadal, Ernest Reguart, Noemí García Aznar, José Manuel Alcaraz Casademunt, Jordi |
Keywords: | Epigenètica Càncer de pulmó Fibroblasts Epigenetics Lung cancer Fibroblasts |
Issue Date: | 26-Dec-2022 |
Publisher: | Springer Nature |
Abstract: | The TGF-β1 transcription factor SMAD3 is epigenetically repressed in tumour-associated fibroblasts (TAFs) from lung squamous cell carcinoma (SCC) but not adenocarcinoma (ADC) patients, which elicits a compensatory increase in SMAD2 that renders SCC-TAFs less fibrotic. Here we examined the effects of altered SMAD2/3 in fibroblast migration and its impact on the desmoplastic stroma formation in lung cancer.We used a microfluidic device to examine descriptors of early protrusions and subsequent migration in 3D collagen gels upon knocking down SMAD2 or SMAD3 by shRNA in control fibroblasts and TAFs.High SMAD3 conditions as in shSMAD2 fibroblasts and ADC-TAFs exhibited a migratory advantage in terms of protrusions (fewer and longer) and migration (faster and more directional) selectively without TGF-β1 along with Erk1/2 hyperactivation. This enhanced migration was abrogated by TGF-β1 as well as low glucose medium and the MEK inhibitor Trametinib. In contrast, high SMAD2 fibroblasts were poorly responsive to TGF-β1, high glucose and Trametinib, exhibiting impaired migration in all conditions.The basal migration advantage of high SMAD3 fibroblasts provides a straightforward mechanism underlying the larger accumulation of TAFs previously reported in ADC compared to SCC. Moreover, our results encourage using MEK inhibitors in ADC-TAFs but not SCC-TAFs. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41416-022-02093-x |
It is part of: | British Journal of Cancer, 2022, vol. 128, num. 6, p. 967-981 |
URI: | https://hdl.handle.net/2445/193843 |
Related resource: | https://doi.org/10.1038/s41416-022-02093-x |
ISSN: | 1532-1827 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) Articles publicats en revistes (Biomedicina) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
2022_BriJouCan_3Dcollagen_AlcarazJ.pdf | 4.85 MB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License