Some of our publications. Find here for the complete list

Identification of a novel alternative splicing isoform of the Hippo kinase STK3/MST2 with impaired kinase and cell growth suppressing activities. Oncogene (2024). 10.1038/s41388-024-03104-2 Rodrigues AM, Paula Zen Petisco Fiore A, Guardia GDA, Tomasin R, Azevedo Reis Teixeira A, Giordano RJ, Schechtman D, Pagano M, Galante PAF, Bruni-Cardoso A.   We identified a new splicing variant of STK3/MST2 (delta 7) in cultured malignant cells and validated that it is almost exclusively expressed in cancer samples from patients. Delta 7 results in a protein that is more ubiquitylated and presents impaired kinase activity and ability to induce cell cycle arrest and cell death.

A molecular landscape of quiescence and proliferation highlights the role of Pten in mammary gland acinogenesis. Tomasin R, Rodrigues AM, Manucci AC, Bruni-Cardoso A. J Cell Sci (2023) 136 (19): jcs261178  10.1242/jcs.261178 . In this work, we demonstrated that quiescence has multiple layers of regulation (RNA and protein levels, as well as posttranslational modifications) in several pathways, which is consistent with the resilience of the quiescent state. Interestingly, quiescent cells do receive and sense extracellular proliferative signals, but these signals get shut down, and therefore there is no proliferation. Pten is upregulated in quiescent cells and acts as a disrupting node between upstream signaling and downstream effectors. 

Extracellular matrix stiffness regulates degradation of MST2 via SCF βTrCP. Biochim Biophys Acta Gen Subj. 2022 Aug 28;1866(12):130238   10.1016/j.bbagen.2022.130238 . Fiore APZP, Rodrigues AM, Ribeiro-Filho HV, Manucci AC, de Freitas Ribeiro P, Botelho MCS, Vogel C, Lopes-de-Oliveira PS, Pagano M, Bruni-Cardoso A. . In this work, demonstrated that MST2, a core Hippo kinase, is degraded by the ubiquitin-proteasome system in a process mediated by the E3-ligase complex SCF βTrCP, which binds MST2 via a non-canonical degradation motif. We found that this process was activated in mammary epithelial cells by stiff extracellular matrix and integrin hyperactivation.

Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas. Neoplasia. 2022 Aug;30:100803   10.1016/j.neo.2022.100803 .Cerqueira OLD, Botelho MCS, Fiore APZP, Osório CABT, Tomasin R, Morais MCC, López RVM, Cardoso EC, Vilella-Arias SA, Reis EM, Bruni-Cardoso A. .In this article, we showed integrin αV is a putative prognostic marker of breast cancer. However not only integrin αVexpression but also its localization must be considered to predict patient survival.

Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6. Cell Rep. 2017 Jun 6;19(10):2102-2115  10.1016/j.celrep.2017.05.050 Fiore APZP, Spencer VA, Mori H, Carvalho HF, Bissell MJ, Bruni-Cardoso A.   We demonstrated that malignant cells do not respond to the quiescence-inducing signals from laminin in a mechanism mediated by nuclear actin. This was a pioneering work demonstrating the involvement of nuclear actin in malignancy.