YWHAZ promotes ovarian cancer metastasis by modulating glycolysis

YWHAZ 通过调节糖酵解促进卵巢癌转移

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作者:Jie Shi, Jun Ye, He Fei, Shu-Hen Jiang, Zhi-Yong Wu, Ya-Ping Chen, Li-Wen Zhang, Xiao-Mei Yang

Abstract

Ovarian cancer is one of the three most deadly gynecological cancers, with the highest mortality rate. As the main cause of death, metastasis is considered to be a crucial factor that reduces the survival time of ovarian carcinoma patients. YWHAZ (also known as 14‑3‑3ζ) influences diverse vital cellular processes such as metabolism, signal transduction, apoptosis and cell cycle regulation. In the present study, we determined that YWHAZ is upregulated in ovarian cancers in contrast to normal tissues by immunohistochemical staining. High YWHAZ expression was found to be associated with TNM stage and metastasis‑free prognosis of ovarian cancer patients. Silencing of YWHAZ inhibited the proliferation and facilitated serum starvation‑induced apoptosis of ovarian cancer cells. Cell migration was also suppressed by YWHAZ silencing. Furthermore, using an in vivo metastatic model, we found that YWHAZ silence also inhibited ovarian cancer metastasis in vivo. Notably, glycolysis was clearly inhibited in YWHAZ‑silenced ovarian cancer cells as determined by lactate production assay and Seahorse XF analysis. YWHAZ also regulated the PI3K/Akt1/vimentin signaling pathway in ovarian cancer cells as detected by western blot analysis. Taken together, our results demonstrated that YWHAZ plays an important role in the progression of ovarian cancer and can be used as a potential target for the diagnosis and treatment of epithelial ovarian cancer.

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