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.

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

“…When YAP is dephosphorylated, it is transported to the nucleus where it activates downstream factors. CTGF (connective tissue growth factor), one downstream effector protein of YAP 44, promotes fibroblast proliferation and collagen deposition 45 (Fig. 3A).…”

Association between AXL, Hippo Transducers, and Survival Outcomes in Male Breast Cancer

“…Two investigators (ADB and MM) evaluated immunoreactivity. The modalities used for assessing TAZ, YAP, CTGF, hormone receptors and Ki‐67 levels were detailed elsewhere (Shaaban et al, ; Di Benedetto et al, ).…”

“…In MBC, we have previously reported that the expression of TAZ/YAP and their established target CTGF conferred inferior survival outcomes (Di Benedetto et al, ). To provide further insights into the oncogenic role of TAZ/YAP in such an uncommon tumor, we herein assessed AXL, a member of the TAM family of receptor tyrosine kinases (RTKs) (Graham et al, ), as the Axl gene is a direct target of the Hippo transcriptional machinery (Azzolin et al, ; Zanconato et al, ).…”

FOXC2 positively regulates YAP signaling and promotes the glycolysis of nasopharyngeal carcinoma

“…Then, YAP translocates to the nucleus, where it forms a complex with TEAD and regulates the expression of multiple genes [6][7][8]. Numerous studies have shown the up-regulation of YAP in the tumors, such as liver cancer, breast cancer and so on [9][10][11][12]. It has been reported that the expression of TAZ is positively regulated by EBV-LMP1 and contributes to cell proliferation and epithelial-mesenchymal transition in NPC [13].…”