Cyclin dependent kinase 14 as a paclitaxel-resistant marker regulated by the TGF-β signaling pathway in human ovarian cancer

Guan, Wencai; Yuan, Jia; Li, Xin; Gao, Xuzhu; Wang, Fanchen; Liu, Huiqiang; Shi, Jimin; Xu, Guoxiong

doi:10.7150/jca.86842

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J Cancer 2023; 14(13):2538-2551. doi:10.7150/jca.86842 This issue Cite

Research Paper

Cyclin dependent kinase 14 as a paclitaxel-resistant marker regulated by the TGF-β signaling pathway in human ovarian cancer

Wencai Guan^1*, Jia Yuan^1,2*, Xin Li^1,2, Xuzhu Gao¹, Fanchen Wang^1,2, Huiqiang Liu^1,2, Jimin Shi¹, Guoxiong Xu^1,2✉

1. Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, China;
2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
*These authors share first authorship

Citation:

Guan W, Yuan J, Li X, Gao X, Wang F, Liu H, Shi J, Xu G. Cyclin dependent kinase 14 as a paclitaxel-resistant marker regulated by the TGF-β signaling pathway in human ovarian cancer. J Cancer 2023; 14(13):2538-2551. doi:10.7150/jca.86842. https://www.jcancer.org/v14p2538.htm

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Abstract

Cyclin dependent kinase 14 (CDK14) plays a central role in the control of cell proliferation and cell cycle progression. However, the specific function and regulatory mechanism of CDK14 on paclitaxel (PTX) resistance in ovarian cancer (OC) remain unclear. The present study demonstrated that CDK14 was overexpressed in OC tissues and cells at mRNA and protein levels detected by qRT-PCR, Western blot, and immunohistochemistry. Survival analysis showed that elevated CDK14 was related to the poor prognosis of OC patients. Overexpression of CDK14 was correlated with chemoresistance in OC. The expression level of CDK14 was higher in PTX-resistant OC cells (SK3R-PTX and OV3R-PTX) than in their counterpart-sensitive cells (SK-OV-3 and OVCAR-3). Knockdown of CDK14 decreased multidrug resistance 1 (MDR1) and β-catenin expression in SK3R-PTX and OV3R-PTX cells and resensitized OC cells to PTX by decreasing cell proliferation and inducing cell apoptosis. Administration of transforming growth factor (TGF)-β1 decreased CDK14 protein in PTX-resistant OC cells. The inhibitory effect of TGF-β1 on CDK14 expression was abolished in the presence of a TGF-β type I receptor kinase inhibitor (SB-431542). Furthermore, TGF-β signal transducer Smad2 protein directly bound to the region -437 to -446 upstream of the CDK14 transcription start site (TSS), resulting in downregulating the expression of CDK14. These data indicate that CDK14 is a PTX-resistant marker and is regulated by the TGF-β signaling pathway. Targeting CDK14 to enhance the sensitivity of PTX may provide a new therapeutic strategy for reversing the PTX resistance in OC.

Keywords: CDK14, chemoresistance, ovarian cancer, reversal, TGF-β signal

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APA

Guan, W., Yuan, J., Li, X., Gao, X., Wang, F., Liu, H., Shi, J., Xu, G. (2023). Cyclin dependent kinase 14 as a paclitaxel-resistant marker regulated by the TGF-β signaling pathway in human ovarian cancer. Journal of Cancer, 14(13), 2538-2551. https://doi.org/10.7150/jca.86842.

ACS

Guan, W.; Yuan, J.; Li, X.; Gao, X.; Wang, F.; Liu, H.; Shi, J.; Xu, G. Cyclin dependent kinase 14 as a paclitaxel-resistant marker regulated by the TGF-β signaling pathway in human ovarian cancer. J. Cancer 2023, 14 (13), 2538-2551. DOI: 10.7150/jca.86842.

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CSE

Guan W, Yuan J, Li X, Gao X, Wang F, Liu H, Shi J, Xu G. 2023. Cyclin dependent kinase 14 as a paclitaxel-resistant marker regulated by the TGF-β signaling pathway in human ovarian cancer. J Cancer. 14(13):2538-2551.

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