The Hippo transducers TAZ/YAP and their target CTGF in male breast cancer.

Abstract

Male breast cancer (MBC) is a rare disease and its biology is poorly understood. Deregulated Hippo pathway promotes oncogenic functions in female breast cancer. We herein investigated the expression of the Hippo transducers TAZ/YAP and their target CTGF in MBC. Tissue microarrays containing samples from 255 MBC patients were immunostained for TAZ, YAP and CTGF. One hundred and twenty-nine patients were considered eligible. The Pearson's Chi-squared test of independence was used to test the association between categorical variables. The correlation between TAZ, YAP and CTGF was assessed with the Pearson's correlation coefficient. The Kaplan-Meier method and the log-rank test were used for estimating and comparing survival curves. Cox proportional regression models were built to identify variables impacting overall survival. Statistical tests were two-sided. Tumors were considered to harbor active TAZ/YAP-driven gene transcription when they co-expressed TAZ, or YAP, and CTGF. Patients whose tumors had the TAZ/CTGF and YAP/CTGF phenotypes experienced shorter overall survival compared with their negative counterparts (log rank p = 0.036 for both). TAZ/CTGF and YAP/CTGF tumors were associated with decreased survival in patients with invasive ductal carcinomas, G3 tumors, hormone receptor-positive tumors, and tumors with elevated Ki-67. Multivariate analyses confirmed that the TAZ/CTGF and YAP/CTGF phenotypes are independent predictors of survival (HR 2.03, 95% CI: 1.06-3.90, p = 0.033; and HR 2.00, 95% CI: 1.04-3.84, p = 0.037 respectively). Comparable results were obtained when excluding uncommon histotypes (TAZ/CTGF: HR 2.34, 95% CI: 1.16-4.73, p = 0.018. YAP/CTGF. HR 2.36, 95% CI: 1.17-4.77, p = 0.017). Overall, the TAZ/YAP-driven oncogenic program may be active in MBC, conferring poorer survival.

• Authors: Anna Di Benedetto, Marcella Mottolese, Francesca Sperati, Cristiana Ercolani, Luigi Di Lauro, Laura Pizzuti, Patrizia Vici, Irene Terrenato, Isabella Sperduti, Abeer M Shaaban, Sreekumar Sundara-Rajan, Maddalena Barba, Valerie Speirs, Ruggero De Maria, Marcello Maugeri-Saccà
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 28 Pg. 43188-43198 (Jul 12 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27248471 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• CCN2 protein, human
• Intracellular Signaling Peptides and Proteins
• Ki-67 Antigen
• Phosphoproteins
• Receptors, Steroid
• Trans-Activators
• Transcription Factors
• Transcriptional Coactivator with PDZ-Binding Motif Proteins
• WWTR1 protein, human
• YAP-Signaling Proteins
• YAP1 protein, human
• Connective Tissue Growth Factor
• Protein Serine-Threonine Kinases

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Adult
• Aged
• Aged, 80 and over
• Breast Neoplasms, Male (genetics, mortality, pathology)
• Carcinogenesis (genetics)
• Carcinoma, Ductal, Breast (genetics, mortality, pathology)
• Connective Tissue Growth Factor (metabolism)
• Gene Expression Regulation, Neoplastic
• Hippo Signaling Pathway
• Humans
• Immunohistochemistry
• Intracellular Signaling Peptides and Proteins (metabolism)
• Kaplan-Meier Estimate
• Ki-67 Antigen (metabolism)
• Male
• Middle Aged
• Neoplasm Grading
• Phenotype
• Phosphoproteins (metabolism)
• Proportional Hazards Models
• Protein Serine-Threonine Kinases (metabolism)
• Rare Diseases (genetics, mortality, pathology)
• Receptors, Steroid (metabolism)
• Retrospective Studies
• Signal Transduction (genetics)
• Tissue Array Analysis
• Trans-Activators
• Transcription Factors
• Transcriptional Coactivator with PDZ-Binding Motif Proteins
• YAP-Signaling Proteins