6533b836fe1ef96bd12a1344
RESEARCH PRODUCT
TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells
Alfredo PagliucaMatilde TodaroMarcello Maugeri-saccàEmanuela PilozziA Di BenedettoMarcella MottoleseFrancesca SperatiGiulia FedericiM PatriziiStefano PiccoloChiara MoriconiGiorgio StassiRosanna DattiloMonica BartucciMarco BiffoniR De MariaMaria Ida Amabilesubject
cancer stem cellsTAZAnimals; 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 AssaysCancer ResearchBioinformaticschemotherapyMetastasistaz; breast cancerMiceNeoplasm Metastasiseducation.field_of_studyTumorIntracellular Signaling Peptides and ProteinsCell cycleGene Expression Regulation NeoplasticLocalNeoplastic Stem Cellsbreast cancer; cancer stem cells; chemotherapy; metastasis; TAZ; Animals; Biomarkers Tumor; Breast Neoplasms; Cell Line Tumor; Disease-Free Survival; Female; Gene Expression Regulation Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Mice; Neoplasm Metastasis; Neoplasm Recurrence Local; Neoplastic Stem Cells; Xenograft Model Antitumor Assays; Molecular Biology; Genetics; Cancer ResearchFemaleStem cellPopulationBreast NeoplasmsBiologyDisease-Free SurvivalCell Linebreast cancer cancer stem cells TAZBreast cancerbreast cancerCancer stem cellSettore MED/04 - PATOLOGIA GENERALECell Line TumormedicineBiomarkers TumorGeneticsmetastasisAnimalsHumanseducationMolecular BiologyHippo signaling pathwayNeoplasticCancermedicine.diseaseXenograft Model Antitumor AssaysNeoplasm RecurrenceGene Expression RegulationTranscriptional Coactivator with PDZ-Binding Motif ProteinsCancer researchTrans-ActivatorsNeoplasm Recurrence LocalBiomarkersTranscription Factorsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 |