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dc.contributor.authorEritja Sánchez, Núria
dc.contributor.authorNavaridas Fernández de Bobadilla, Raúl
dc.contributor.authorRuiz Mitjana,Anna
dc.contributor.authorVidal Sabanés, Maria
dc.contributor.authorEgea Navarro, Joaquim
dc.contributor.authorEncinas Martín, Mario
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorDolcet Roca, Xavier
dc.description.abstractTGF-β has a dichotomous function, acting as tumor suppressor in premalignant cells but as a tumor promoter for cancerous cells. These contradictory functions of TGF-β are caused by different cellular contexts, including both intracellular and environmental determinants. The TGF-β/SMAD and the PI3K/PTEN/AKT signal transduction pathways have an important role in the regulation of epithelial cell homeostasis and perturbations in either of these two pathways' contributions to endometrial carcinogenesis. We have previously demonstrated that both PTEN and SMAD2/3 display tumor-suppressive functions in the endometrium, and genetic ablation of either gene results in sustained activation of PI3K/AKT signaling that suppresses TGF-β-induced apoptosis and enhances cell proliferation of mouse endometrial cells. However, the molecular and cellular effects of PTEN deficiency on TGF-β/SMAD2/3 signaling remain controversial. Here, using an in vitro and in vivo model of endometrial carcinogenesis, we have demonstrated that loss of PTEN leads to a constitutive SMAD2/3 nuclear translocation. To ascertain the function of nuclear SMAD2/3 downstream of PTEN deficiency, we analyzed the effects of double deletion PTEN and SMAD2/3 in mouse endometrial organoids. Double PTEN/SMAD2/3 ablation results in a further increase of cell proliferation and enlarged endometrial organoids compared to those harboring single PTEN, suggesting that nuclear translocation of SMAD2/3 constrains tumorigenesis induced by PTEN deficiency.
dc.description.sponsorshipThis research was supported by grants SAF2016-80157-R and PID2019-104734RB-I00 from Spanish Ministerio de Ciencia, Innovación y Universidades, Grupos estables de la Asociación Española Contra el Cancer, AECC
dc.relation.isformatofReproducció del document publicat a :
dc.relation.ispartofCancers, 2021, vol. 13, núm. 19, p. 4990
dc.rightscc-by (c) autors, 2021
dc.subjectEndometrial cancer
dc.titleEndometrial PTEN Deficiency Leads to SMAD2/3 Nuclear Translocation

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