STAT3 phosphorylation at serine 727 activates specific genetic programs and promotes clear cell renal cell carcinoma (ccRCC) aggressiveness
Arévalo, Jazmine (Vall d'Hebron Institut de Recerca (VHIR))
Campoy, I. (Vall d'Hebron Institut de Recerca (VHIR))
Durán, Mónica (Vall d'Hebron Institut de Recerca (VHIR))
Nemours, Stéphane (Biodonostia Osasun Ikerketako Institutura (País Basc))
Areny, A. (Vall d'Hebron Institut de Recerca (VHIR))
Vall-Palomar, M. (Vall d'Hebron Institut de Recerca (VHIR))
Martínez, C. (Institut de Recerca Biomèdica de Lleida)
Cantero-Recasens, Gerard (Vall d'Hebron Institut de Recerca (VHIR))
Meseguer Navarro, Anna (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2023
Resum:	The signal transducer and activator of transcription 3 (STAT3) is a transcription factor mainly activated by phosphorylation in either tyrosine 705 (Y705) or serine 727 (S727) residues that regulates essential processes such as cell differentiation, apoptosis inhibition, or cell survival. Aberrant activation of STAT3 has been related to development of nearly 50% of human cancers including clear cell renal cell carcinoma (ccRCC). In fact, phosho-S727 (pS727) levels correlate with overall survival of ccRCC patients. With the aim to elucidate the contribution of STAT3 phosphorylation in ccRCC development and progression, we have generated human-derived ccRCC cell lines carrying STAT3 Y705 and S727 phosphomutants. Our data show that the phosphomimetic substitution Ser727Asp facilitates a pro-tumoral phenotype in vitro, in a Y705-phosphorylation-independent manner. Moreover, we describe that STAT3 phosphorylation state determines the expression of different subsets of target genes associated with distinct biological processes, being pS727-dependent genes the most related to cellular hallmarks of cancer. In summary, the present study constitutes the first analysis on the role of overall STAT3 phosphorylation state in ccRCC and demonstrates that pS727 promotes the expression of a specific subset of target genes that might be clinically relevant as novel biomarkers and potential therapeutic targets for ccRCC.
Ajuts:	Ministerio de Economía y Competitividad SAF2014-59945-R Agencia Estatal de Investigación SAF2017-89989-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01600
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cancer models ; Molecular medicine
Publicat a:	Scientific reports, Vol. 13 (November 2023) , art. 19552, ISSN 2045-2322

DOI: 10.1038/s41598-023-46628-5
PMID: 37945711

18 p, 5.8 MB

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