000124354 001__ 124354
000124354 005__ 20241125101128.0
000124354 0247_ $$2doi$$a10.1038/s41416-022-02093-x
000124354 0248_ $$2sideral$$a132682
000124354 037__ $$aART-2023-132682
000124354 041__ $$aeng
000124354 100__ $$0(orcid)0000-0003-2237-8859$$aJuste-Lanas, Y.$$uUniversidad de Zaragoza
000124354 245__ $$a3D collagen migration patterns reveal a SMAD3-dependent and TGF-ß1-independent mechanism of recruitment for tumour-associated fibroblasts in lung adenocarcinoma
000124354 260__ $$c2023
000124354 5060_ $$aAccess copy available to the general public$$fUnrestricted
000124354 5203_ $$aBackground: 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. Methods: 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. Results: 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. Conclusions: 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.
000124354 536__ $$9info:eu-repo/grantAgreement/ES/MICINN-AEI-FEDER/PID2021-122409OB-C21$$9info:eu-repo/grantAgreement/ES/MCIU/FPU17-03867$$9info:eu-repo/grantAgreement/ES/ISCIII PI18-00920$$9info:eu-repo/grantAgreement/ES/ISCIII PI14-01109$$9info:eu-repo/grantAgreement/ES/FIS FEDER/PS09-02368$$9info:eu-repo/grantAgreement/ES/AEI/AEI PID2019-110944RB-I00$$9info:eu-repo/grantAgreement/ES/AEI-FEDER/SAF2016-79527-R$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-094494-B-C21
000124354 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000124354 590__ $$a6.4$$b2023
000124354 591__ $$aONCOLOGY$$b46 / 322 = 0.143$$c2023$$dQ1$$eT1
000124354 594__ $$a15.1$$b2023
000124354 592__ $$a3.0$$b2023
000124354 593__ $$aOncology$$c2023$$dQ1
000124354 593__ $$aCancer Research$$c2023$$dQ1
000124354 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000124354 700__ $$aDíaz-Valdivia, N.
000124354 700__ $$aLlorente, A.
000124354 700__ $$aIkemori, R.
000124354 700__ $$aBernardo, A.
000124354 700__ $$aArshakyan, M.
000124354 700__ $$0(orcid)0000-0002-3784-1140$$aBorau, C.$$uUniversidad de Zaragoza
000124354 700__ $$aRamírez, J.
000124354 700__ $$aRuffinelli, J. C.
000124354 700__ $$aNadal, E.
000124354 700__ $$aReguart, N.
000124354 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía-Aznar, J. M.$$uUniversidad de Zaragoza
000124354 700__ $$aAlcaraz, J.
000124354 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000124354 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000124354 773__ $$g128 (2023), 967-981$$pBr. J. Cancer$$tBRITISH JOURNAL OF CANCER$$x0007-0920
000124354 8564_ $$s4951653$$uhttps://zaguan.unizar.es/record/124354/files/texto_completo.pdf$$yVersión publicada
000124354 8564_ $$s2655535$$uhttps://zaguan.unizar.es/record/124354/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000124354 909CO $$ooai:zaguan.unizar.es:124354$$particulos$$pdriver
000124354 951__ $$a2024-11-22-11:58:17
000124354 980__ $$aARTICLE