Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast
| العنوان: | Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast |
|---|---|
| المؤلفون: | Simona Nuzzo, Federica Benvenuti, Alessandra Rustighi, Vincenzo Eterno, Antonio Rosato, Alessandro Zannini, Luca Tiberi, Roberta Sommaggio, Giannino Del Sal, Iannis Aifantis, Antonella Tuscano, Silvio Bicciato, Giovanni Sorrentino, Silvano Piazza, Alberto Zambelli, Libero Santarpia |
| المساهمون: | Rustighi, Alessandra, Zannini, Alessandro, Tiberi, Luca, Sommaggio, Roberta, Piazza, Silvano, Sorrentino, Giovanni, Nuzzo, Simona, Tuscano, Antonella, Eterno, Vincenzo, Benvenuti, Federica, Santarpia, Libero, Aifantis, Ianni, Rosato, Antonio, Bicciato, Silvio, Zambelli, Alberto, DEL SAL, Giannino |
| المصدر: | EMBO Molecular Medicine EMBO molecular medicine, 6 (1 Europe PubMed Central |
| بيانات النشر: | BlackWell Publishing Ltd, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Ubiquitin-Protein Ligase, F-Box-WD Repeat-Containing Protein 7, Cell Cycle Proteins, Triple Negative Breast Neoplasms, Stem cells, Mice, SCID, Metastasis, Antineoplastic Agent, Mice, Breast cancer, Receptors, Cell Cycle Protein, Transplantation, Heterologou, Receptor, Notch1, Receptor, Notch4, Research Articles, cancer cell, Mice, Knockout, Heterologous, Proto-Oncogene Protein, Tumor, Receptors, Notch, Peptidylprolyl Isomerase, Mammary Glands, 3. Good health, stem cells, Neoplastic Stem Cells, Fbxw7 E3 ubiquitin-ligase, Molecular Medicine, Female, Stem cell, Corrigendum, Breast Neoplasm, Receptor, Human, Signal Transduction, Notch, Prolyl-isomerase Pin1, Animals, Antineoplastic Agents, Breast Neoplasms, Cell Line, Tumor, F-Box Proteins, Humans, Mammary Glands, Human, Proto-Oncogene Proteins, Stem Cells, Transplantation, Heterologous, Ubiquitin-Protein Ligases, Knockout, Triple Negative Breast Neoplasm, Notch signaling pathway, Biology, SCID, Cell Line, Cancer stem cell, Stem Cell, medicine, F-Box Protein, Peptidylprolyl isomerase, Notch1, Transplantation, Animal, Biologie moléculaire, medicine.disease, NIMA-Interacting Peptidylprolyl Isomerase, Immunology, Cancer cell, Cancer research, Neoplastic Stem Cell |
| الوصف: | Mammary epithelial stem cells are fundamental to maintain tissue integrity. Cancer stem cells (CSCs) are implicated in both treatment resistance and disease relapse, and the molecular bases of their malignant properties are still poorly understood. Here we show that both normal stem cells and CSCs of the breast are controlled by the prolyl-isomerase Pin1. Mechanistically, following interaction with Pin1, Notch1 and Notch4, key regulators of cell fate, escape from proteasomal degradation by their major ubiquitin-ligase Fbxw7α. Functionally, we show that Fbxw7α acts as an essential negative regulator of breast CSCs' expansion by restraining Notch activity, but the establishment of a Notch/Pin1 active circuitry opposes this effect, thus promoting breast CSCs self-renewal, tumor growth and metastasis in vivo. In human breast cancers, despite Fbxw7α expression, high levels of Pin1 sustain Notch signaling, which correlates with poor prognosis. Suppression of Pin1 holds promise in reverting aggressive phenotypes, through CSC exhaustion as well as recovered drug sensitivity carrying relevant implications for therapy of breast cancers. © 2013 The Authors. SCOPUS: ar.j info:eu-repo/semantics/published |
| وصف الملف: | STAMPA; 1 full-text file(s): application/pdf |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5118bdcb4935ce7e386cbd46c4b60606Test http://europepmc.org/articles/PMC4023890Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5118bdcb4935ce7e386cbd46c4b60606 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17574684 17574676 |
|---|