Up-regulation of MELK by E2F1 promotes the proliferation in cervical cancer cells

Cervical cancer is a common gynecologic cancer and a frequent cause of death. In this study, we investigated the role of MELK (maternal embryonic leucine zipper kinase) in cervical cancer. We found that HPV 18 E6/E7 promoted MELK expression by activating E2F1. MELK knockdown blocked cancer cells growth. Furthermore, we used MELK-8A to inhibit the kinase activity of MELK and caused the G2/M phase arrest of cancer cells. Under the treatment of inhibitors, Hela cells formed multipolar spindles and eventually underwent apoptosis. We also found that MELK is involved in protein translation and folding during cell division through the MELK interactome and the temporal proteomic analysis under inhibition with MELK-8A. Altogether, these results suggest that MELK may play a vital role in cancer cell proliferation and indicate a potential therapeutic target for cervical cancer.

 

Comments:

The study you described investigated the role of MELK (maternal embryonic leucine zipper kinase) in cervical cancer. The researchers discovered that HPV 18 E6/E7, which are viral proteins associated with cervical cancer development, promoted the expression of MELK by activating a transcription factor called E2F1.

By conducting experiments in cancer cells, the researchers demonstrated that knocking down MELK expression inhibited the growth of cancer cells. Additionally, they utilized a compound called MELK-8A to inhibit the kinase activity of MELK, which led to the arrest of cancer cells in the G2/M phase of the cell cycle. This indicates that MELK is involved in regulating cell division.

Under the treatment with MELK-8A, the researchers observed that Hela cells (a cervical cancer cell line) formed multipolar spindles, which are abnormal structures involved in cell division. This ultimately led to the induction of apoptosis, a form of programmed cell death.

The study also investigated the broader role of MELK in cellular processes by analyzing its interactome (the proteins it interacts with) and conducting temporal proteomic analysis (analyzing protein changes over time) under the inhibition of MELK with MELK-8A. The results suggested that MELK is involved in protein translation and folding during cell division, indicating its importance in various cellular processes.

Overall, the findings from this study suggest that MELK plays a crucial role in cancer cell proliferation, particularly in cervical cancer. The results highlight MELK as a potential therapeutic target for cervical cancer treatment.

Related Products

Cat.No.	Product Name	Information
S0430	MELK-8a Dihydrochloride	MELK-8a Dihydrochloride is a novel inhibitor of maternal embryonic leucine zipper kinase (MELK) with an IC50 of 2 nM.

Related Targets

MELK