دورية أكاديمية
Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer
| العنوان: | Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer |
|---|---|
| المؤلفون: | Mónica Álvarez-Fernández, María Sanz-Flores, Belén Sanz-Castillo, Salazar Roa, María, David Partida, Elisabet Zapatero-Solana, H. Raza Ali, Eusebio Manchado, Scott Lowe, Todd VanArsdale, David Shields, Carlos Caldas, Miguel Quintela-Fandino, Marcos Malumbres |
| المساهمون: | Marcos Malumbres |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2017 |
| المجموعة: | Universidad Complutense de Madrid (UCM): E-Prints Complutense |
| مصطلحات موضوعية: | Cell cycle, MASTL, PP2A, Biología celular (Biología), 2403 Bioquímica |
| الوصف: | PP2A is a major tumor suppressor whose inactivation is frequently found in a wide spectrum of human tumors. In particular, deletion or epigenetic silencing of genes encoding the B55 family of PP2A regulatory subunits is a common feature of breast cancer cells. A key player in the regulation of PP2A/B55 phosphatase complexes is the cell cycle kinase MASTL (also known as Greatwall). During cell division, inhibition of PP2A-B55 by MASTL is required to maintain the mitotic state, whereas inactivation of MASTL and PP2A reactivation is required for mitotic exit. Despite its critical role in cell cycle progression in multiple organisms, its relevance as a therapeutic target in human cancer and its dependence of PP2A activity is mostly unknown. Here we show that MASTL overexpression predicts poor survival and shows prognostic value in breast cancer patients. MASTL knockdown or knockout using RNA interference or CRISPR/Cas9 systems impairs proliferation of a subset of breast cancer cells. The proliferative function of MASTL in these tumor cells requires its kinase activity and the presence of PP2A-B55 complexes. By using a new inducible CRISPR/Cas9 system in breast cancer cells, we show that genetic ablation of MASTL displays a significant therapeutic effect in vivo. All together, these data suggest that the PP2A inhibitory kinase MASTL may have both prognostic and therapeutic value in human breast cancer. ; Depto. de Bioquímica y Biología Molecular ; Fac. de Ciencias Biológicas ; TRUE ; pub |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1350-9047 1476-5403 |
| العلاقة: | info:eu-repo/grantAgreement/MINECO//SAF2014-60442-JIN/ES/RELEVANCIA FUNCIONAL DE LA RUTA GREATWALL%2FPP2A EN EL MANTENIMIENTO DE LA ESTABILIDAD GENOMICA: IMPLICACIONES TERAPEUTICAS EN CANCER/; SAF2012-38215; info:eu-repo/grantAgreement/MINECO//SAF2014-57791-REDC/ES/BIOLOGIA DEL CANCER/; OncoCycle Programme (S2010/BMD-2470); MitoSys project; HEALTH-F5-2010-241548); https://hdl.handle.net/20.500.14352/97839Test; Álvarez-Fernández, M., Sanz-Flores, M., Sanz-Castillo, B. et al. Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer. Cell Death Differ (2017). https://doi.org/10.1038/s41418-017-0024-0Test; https://www.nature.com/articles/s41418-017-0024-0Test |
| DOI: | 10.1038/s41418-017-0024-0 |
| الإتاحة: | https://doi.org/20.500.14352/97839Test https://doi.org/10.1038/s41418-017-0024-0Test https://hdl.handle.net/20.500.14352/97839Test https://www.nature.com/articles/s41418-017-0024-0Test |
| حقوق: | open access |
| رقم الانضمام: | edsbas.4FD360B4 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 13509047 14765403 |
|---|---|
| DOI: | 10.1038/s41418-017-0024-0 |