The Correlation Between Hippo-YAP/TAZ Signaling Pathway And Triple Negative Breast Cancer

Objective:Breast cancer has become one of the common malignancies and threaten women's health today.According to the epidemiological statistics,the incidence and mortality of breast cancer have increased year by year in China.Triple-negative breast cancer(TNBC)is a subtype of breast cancer,which refers to the negative expression of ER,PR and HER-2.Due to lack of antagonistic hormone and anti-HER2 therapy targets,there is not an effective treatment for TNBC.Thus,TNBC has a very poor prognosis.Therefore,exploring and discovering new targeted therapies and molecules has become an urgent task to improve the treatment efficiency of TNBC.Previous studies indicate that Hippo-YAP/TAZ signaling pathway plays an important role in the development of many malignant tumors.This research focuses on the role of Hippo-YAP/TAZ signaling pathway in TNBC and identifies the Hippo-YAP/TAZ signaling pathway as a targeting pathway for diagnosis and therapy of TNBC.Methods:1?The mRNA levels of YAP,TAZ,CYR61 and CTGF in triple-negative breast cancer MDA-MB-231 cells and non-negative breast cancer MCF7 cells were determined by RT-qPCR.2?The expression and localization of YAP and TAZ in triple-negative breast cancer MDA-MB-231 cells and non-negative breast cancer MCF7 cells were detected by cell immunofluorescence after LPA stimulation.3 ? Established YAP-knockdown cell lines in triple-negative breast cancer MDA-MB-231 cells using lentiviral vector-loaded YAP shRNA,and determined the knockdown effect on cell proliferation.4?Samples of breast cancer tissue(including 109 cases of triple-negative breastcancer and 140 cases of non-triple negative breast cancer)and the corresponding clinical data were collected,and their pathological characteristics were statistically analyzed.5?Expression of the Hippo-YAP/TAZ signaling pathway proteins YAP,TAZ and the downstream target gene product CYR61 in 109 triple-negative and 140 non-triple negative breast cancers was examed by immunohistochemical staining(IHC)using tissue microarray assay(TMA).Statistical analysis of the association of YAP,TAZ,CYR61 expression with triple negative breast cancer.Results:1?The mRNA levels of YAP,TAZ,CYR61 and CTGF in triple-negative breast cancer was significantly higher than that in non-triple negative breast cancer.2?LPA stimulation of triple-negative breast cancer MDA-MB-231 cells can significantly promote the nuclear localization of YAP/TAZ,and this effect was not found in non-triple negative breast cancer MCF7 cells.3?YAP knockdown in triple-negative breast cancer MDA-MB-231 cells significantly inhibited cell proliferation.4?Analysis of clinical data on breast cancer patients showed that patients with triple-negative breast cancer had later clinical stages,larger tumor volumes and more metastatic recurrence than patients with non-triple negative breast cancer.5?Immunohistochemical staining of the tumor tissue microarray of breast cancer showed that the positive rate of YAP,TAZ and CYR61 in triple-negative breast cancer tissues was significantly higher than that in non-triple negative breast cancer tissues.Conclusions:The Hippo-YAP/TAZ signal of triple-negative breast cancer cells was significantly stronger than that of non-triple negative breast cancer cells,and knockdown of YAP inhibited the proliferation of triple-negative breast cancer cells,indicating that the Hippo-YAP/TAZ signaling pathway plays an important role in the proliferation of triple-negative breast cancer cells.Triple-negative breast cancer has later clinical stages,larger tumors,and poorer prognosis than non-triple negative breast cancer.Expression of the of Hippo-YAP/TAZ signaling pathway proteins YAP and TAZ and the downstream target gene CYR61 and CTGF in triple-negative breast cancer was significantly higher than those in non-triple negative breast cancer,indicating that the Hippo-YAP/TAZ signaling pathway was significantly correlated with the triple-negative breast cancer.Our studies suggests that Hippo-YAP/TAZ signaling pathway is a major signaling pathway in triple-negative breast cancer,and it could be an effective targeting pathway for therapy of triple-negative breast cancer.