GTSE1: a novel TEAD4-E2F1 target gene involved in cell protrusions formation in triple-negative breast cancer cell models
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Debora Stelitano1, Yamila Peche Leticia1, Emiliano Dalla1, Martin Monte2, Silvano Piazza1,3 and Claudio Schneider1,4
1Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie (L.N.CIB), Trieste, Italy
2Laboratorio de Oncología Molecular, Departamento de Química Biológica and IQUIBICEN-UBA/CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina
3Bioinformatics Core facility, Centre for Integrative Biology, University of Trento (CIBIO), Trento, Italy
4Dipartimento di Scienze Biomediche e Biologiche (DSMB), Università degli Studi di Udine, Udine, Italy
Claudio Schneider, email: email@example.com
Silvano Piazza, email: firstname.lastname@example.org
Keywords: GTSE1, TEAD4, E2F1, YAP/TAZ, cell protrusions
Received: November 25, 2016 Accepted: May 22, 2017 Published: June 27, 2017
GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC).
Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1.
Moreover, we found that TEAD4 controls the formation of cell protrusions required for cell migration through GTSE1, unveiling a relevant effector role for this protein in the TEAD-dependent cellular functions and confirming TEAD4 role in promoting invasion and metastasis in breast cancer.
Finally, we highlighted a role for the pRb-E2F1 pathway in the control of GTSE1 transcription and observed that treatment with drugs targeting the pRb-E2F1 or YAP/TAZ-TEAD pathways dramatically downregulated the expression levels of GTSE1 and of other genes involved in the formation of metastasis, suggesting their potential use in the treatment of TNBC.
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