Date: Friday, 6 May 2022

Time: 5:00 p.m. - 6:00 p.m.

Via Zoom: https://hku.zoom.us/j/99246629847?pwd=eHM2N3ExUlRmNGtWOVhDYThVdUV5Zz09

Meeting ID: 992 4662 9847

Password: 946670

5:00 p.m.

Presenter: Mr. Tianzi WEI, PhD candidate
Primary Supervisor: Prof. Dong-Yan JIN
Presentation Title: Epigenetic regulation of the DNMT1/MT1G/KLF4/CA9 axis synergizes the anticancer effects of sorafenib in hepatocellular carcinoma
Abstract: Sorafenib, a multiple-kinase inhibitor, has been widely used as a first-line anticancer drug for advanced hepatocellular carcinoma (HCC). However, the development of drug resistance to sorafenib is frequently observed in clinical applications. Potential non-kinase targets of sorafenib have not been well documented and may provide insights into reversing drug resistance and enhancing drug effectiveness. Herein, we report that sorafenib exerted its anticancer effects by activating metallothionein 1G (MT1G) expression. MT1G served as a novel marker in HCC and correlated well with patient survival. MT1G overexpression suppressed the cellular proliferation, migration, invasion, and tumor formation of HCC, and sensitized cells to sorafenib treatment. However, the disruption of MT1G attenuated sorafenib’s anticancer effects. Mechanistically, sorafenib upregulated MT1G expression via hypomethylation of its promoter region by binding and inhibiting DNA methyltransferase 1 (DNMT1) and increasing its promoter accessibility in HCC cells. The activation of MT1G also inhibited CA9 transcription through the suppression of HIF1α translation as mediated by KLF4. Our collective data revealed that sorafenib exerted its anticancer effects through epigenetic regulation of the DNMT1/MT1G/KLF4/CA9 axis in HCC, and that the activation of MT1G might constitute a strategy for enhancing the effect of sorafenib to suppress HCC cells.

5:30 p.m.

Presenter: Mr.Luyao MA, PhD candidate
Primary Supervisor: Dr. Bo GAO
Presentation Title: Kindlin-2 promotes Src-mediated tyrosine phosphorylation of androgen receptor and contributes to breast cancer progression
Abstract: Breast cancer is one of the most frequently diagnosed cancers worldwide. Recently, androgen receptor (AR) signaling pathway attracted more attention in breast cancer progression. Our result shows that Kindlin-2, a focal adhesion related protein, associates with AR and Src, regulating Src-mediated AR Tyr-534 phosphorylation and further promoting breast cancer progression. Loss of Kindlin-2 suppressed Src-mediated AR Tyr-534 phosphorylation and downstream signaling pathway, inhibiting breast cancer cells migration and proliferation. Re-expression of wild-type Kindlin-2, but not AR-binding-defective or Src-binding-defective mutant forms of Kindlin-2, in Kindlin-2-deficient cells restored AR Tyr-534 phosphorylation, signaling, breast cancer cell proliferation and migration. Finally, ablation of Kindlin-2 from mammary tumors in mouse significantly reduced AR Tyr-534 phosphorylation and downstream signaling pathway.

ALL ARE WELCOME

Should you have any enquiries, please feel free to contact Miss Cynthia Cheung at 3917 9748.