Cyclin-dependent kinase like 3 promotes triple-negative breast cancer progression via inhibiting the p53 signaling pathway
| Autor: | Ya-Ping Zhang, Yong-Ping Liu, Zheng Qian, Zhe Li, Yan-Zhi Bi, Dongxiang Zeng, Gui-Feng Sheng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Triple Negative Breast Neoplasms Protein Serine-Threonine Kinases Flow cytometry Mice Cyclin-dependent kinase Cell Line Tumor medicine Animals Humans Viability assay Triple-negative breast cancer Cell Proliferation Gene knockdown biology medicine.diagnostic_test Cell growth Chemistry Kinase Gene Expression Regulation Neoplastic Oncology Apoptosis Cancer research biology.protein Tumor Suppressor Protein p53 Signal Transduction |
| Zdroj: | Neoplasma. 68(5) |
| ISSN: | 0028-2685 |
| Popis: | It has been reported that cyclin-dependent kinase like 3 (CDKL3) plays a crucial role in cell proliferation and migration in several cancers. However, the function of CDKL3 in triple-negative breast cancer (TNBC) is still unclear. In the present study, immunohistochemistry (IHC) was conducted to detect the CDKL3 expression. CCK-8, flow cytometry, Transwell assays, and mice xenograft models, were performed to explore the roles of CDKL3 on the proliferation and migration of TNBC in vitro and in vivo. Besides, protein chip analysis was used to screen the potential pathways, which was further confirmed by promoter activity assay, western blotting, and CCK-8 assay. Our findings reveal a high expression of CDKL3 in TNBC tissues, which is closely related to a poor prognosis of patients with TNBC. In TNBC cells, CDKL3 knockdown inhibits cell proliferation and migration, whereas CDKL3 overexpression has exactly the opposite effect. Consistently, CDKL3 knockdown induces cell apoptosis in vitro but suppresses tumor growth in vivo. Furthermore, CDKL3 knockdown increases p53 expression and reduces cell viability, and these effects are significantly weakened by the p53 inhibitor, PFT-α. In conclusion, the current study highlights that CDKL3 promotes TNBC progressions via regulating the p53 signaling pathway, suggesting that CDKL3 is a novel therapeutic target for TNBC treatment. |
| Databáze: | OpenAIRE |
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