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TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells
- Publication Year :
- 2015
- Publisher :
- Nature Publishing Group, 2015.
-
Abstract
- Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs is the only cell population endowed with metastatic potential. Gene-expression profile studies comparing metastagenic and non-metastagenic cells identified TAZ, a transducer of the Hippo pathway and biomechanical cues, as a central mediator of BCSCs metastatic ability involved in their chemoresistance and tumorigenic potential. Overexpression of TAZ in low-expressing dBCCs induced cell transformation and conferred tumorigenicity and migratory activity. Conversely, loss of TAZ in BCSCs severely impaired metastatic colonization and chemoresistance. In clinical data from 99 BC patients, high expression levels of TAZ were associated with shorter disease-free survival in multivariate analysis, thus indicating that TAZ may represent a novel independent negative prognostic factor. Overall, this study designates TAZ as a novel biomarker and a possible therapeutic target for BC.
- Subjects :
- cancer stem cells
TAZ
Animals
Biomarkers, Tumor
Breast Neoplasms
Cell Line, Tumor
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Neoplasm Metastasis
Neoplasm Recurrence, Local
Neoplastic Stem Cells
Transcription Factors
Xenograft Model Antitumor Assays
Cancer Research
Bioinformatics
chemotherapy
Metastasis
taz
breast cancer
education.field_of_study
Tumor
Intracellular Signaling Peptides and Proteins
Cell cycle
Local
metastasis
Molecular Biology
Genetics
Stem cell
Population
Biology
Cell Line
breast cancer , cancer stem cells, TAZ
Breast cancer
Cancer stem cell
Settore MED/04 - PATOLOGIA GENERALE
medicine
education
Hippo signaling pathway
Neoplastic
Cancer
medicine.disease
Neoplasm Recurrence
Gene Expression Regulation
Transcriptional Coactivator with PDZ-Binding Motif Proteins
Cancer research
Trans-Activators
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....0ce695d0c23014c417d7f053739d1aad