CDKL5 promotes proliferation, migration, and chemotherapeutic drug resistance of glioma cells via activation of the PI3K/AKT signaling pathway

• Main Authors: Zhenfu Jiang, Tongtong Gong, Hong Wei
• Format: Article
• Language: English
• Published: Wiley 2020-02-01
• Series: FEBS Open Bio
• Subjects: CDKL5; drug resistance; glioma; migration; PI3K; AKT
• Online Access: https://doi.org/10.1002/2211-5463.12780

Gliomas, the most prevalent cancer in the central nervous system, are characterized by high morbidity and mortality, emphasizing the need to understand their etiology. Here, we report that cyclin‐dependent kinase‐like 5 (CDKL5) is highly expressed in gliomas, and CDKL5 overexpression promotes invasion, proliferation, migration and drug (β‐lapachone) resistance of glioma cells. In vitro, CDKL5 overexpression enhanced invasion, growth and migration of glioma cells, and stimulated the phosphoinositide 3‐kinase (PI3K)/AKT axis. Furthermore, CDKL5 overexpression in vivo promoted glioma proliferation, whereas CDKL5 knockdown had opposing effects. The effect of CDKL5 on drug resistance was eliminated if the PI3K/AKT axis was suppressed, and cisplatin combined with the PI3K/AKT suppressor XL147 remarkably prohibited proliferation in xenografts overexpressing CDKL5. Collectively, our findings suggest that CDKL5 acts through the PI3K/AKT axis in glioma cells, and indicate a possible role for CDKL5 in glioma therapy.