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

Abstract

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.

Protein Kinase A–Mediated Effects of Protein Kinase C Partial Agonist 5-(Hydroxymethyl)Isophthalate 1a3 in Colorectal Cancer Cells

“…This information suggests that CDKL2 activation by HMI-1a3 could mediate the observed decrease in viability in colorectal cancer cells. The other three most activated kinases, intestinal cell kinase (ICK) (Whitworth et al, 2012), alpha-protein kinase (AlphaK1) (Chen et al, 2019) and cyclin-dependent kinase-like 5 (CDKL5) (Jiang et al, 2019), are associated with tumour growth and aggressiveness. Being among the most activated kinases, according to the upstream kinase interpretation, cyclic AMP-dependent protein kinase A (PKA) and cyclic GMP-dependent protein kinase G (PKG) also demonstrated high specificity score or consistency in activity on both time points (Tables 1 and 2, Supplementary Figures S3 and S4).…”

Targeting ACLY Attenuates Tumor Growth and Acquired Cisplatin Resistance in Ovarian Cancer by Inhibiting the PI3K–AKT Pathway and Activating the AMPK–ROS Pathway

“…The PI3K–AKT pathway has been well-studied as a molecular escape route for cells to avoid death ( 37 ). In the context of resistance to chemotherapeutic drugs, it is well-known that activation of the PI3K–AKT pathway not only occurs but also has an important role in multidrug resistance ( 38 ). According to Yang et al, AKT promotes resistance to cisplatin in ovarian cancer cell lines by modulating P53 on the caspase-dependent mitochondrial death pathway ( 39 ).…”

LINC00680 Modulates Docetaxel Resistance in Breast Cancer via miR-320b/CDKL5 Axis

“…It was reported that CDKL5 localizes at multiple subcellular structures [26,27], and involved in cell division [26]. The association between CDKL5 and drug resistance was identi ed [28,29]. In vitro experiments suggested that knockdown of CDKL5 and LINC00680 decreased the expression of MDR1, MRP5 and LRP1 (Fig.…”

“…The role of MDR1 and MRP7 in docetaxel resistance were demonstrated in different types of cancer [34][35][36][37]. As shown by Jiang et al [29], CDKL5 promotes chemotherapeutic drug resistance of glioma may through PI3K/AKT pathway. Our study hinted that the expression of CDKL5 and LINC00680 together with chemo-resistance genes MDR1, MRP5 and LRP1 play an important role in docetaxel resistance of breast cancer.…”

“…CDKL5 de ciency or mutations cause a distinct disorder, especially in neuro system because it is expressed throughout the brain starting at late embryonic stages. However, Jiang et., al [8] found that CDKL5 could promote progression and β-lapachone resistance of glioma, Robin et., al [9] indicated CDKL5 presented as prognostic marker for glioblastoma, and Masahiro et., al [10] suggested CDKL5 peptide can be used for cytotoxic T-lymphocyte-mediated immunotherapy, so it's of great interest for us to nd the role of CDKL5 in the progression of breast cancer.Long non-coding RNAs (lncRNAs) is a kind of RNAs with length over 200 nucleotides, and usually described to in uence mRNA generation and expression [11].…”