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

Abstract

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.

• Authors: Hongzhi Sun, Hongmei Ma, Hao Zhang, Minjun Ji
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 17 Issue 14 Pg. 3875-3888 ( 2021) ISSN: 1449-2288 [Electronic] Australia
• PMID: 34671205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• E2F1 Transcription Factor
• E2F1 protein, human
• MELK protein, human
• Protein Serine-Threonine Kinases

Topics

• Animals
• Apoptosis
• Cell Division
• Cell Line, Tumor
• Cell Proliferation
• E2F1 Transcription Factor (metabolism)
• Female
• G2 Phase
• Humans
• Mass Spectrometry
• Mice
• Mice, Nude
• Mitosis
• Protein Binding
• Protein Serine-Threonine Kinases (metabolism)
• Up-Regulation
• Uterine Cervical Neoplasms (metabolism, pathology)
• Xenograft Model Antitumor Assays