Cyclin-dependent kinase like 3 promotes triple-negative breast cancer progression via inhibiting the p53 signaling pathway

Abstract

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 (I HC) 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 pro liferation 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, PFTstudy highlights that CDKL3 promotes TNBC progressions via regulating the p53 signaling pathway, suggesting that CDKL3 is a novel therapeutic target for TNBC treatment.

CDKL3 is a promising biomarker for diagnosis and prognosis prediction in patients with hepatocellular carcinoma

“…Recent studies have investigated the oncogenic role of CDKL3 in various tumors, including glioma [ 6 ], oesophageal squamous cell carcinoma [ 10 ], osteosarcoma [ 11 ], colorectal cancer [ 12 ], breast cancer [ 39 ], and cholangiocarcinoma [ 8 ]. However, the role of CDKL3 in HCC has not been thoroughly examined.…”

Chemical, Biochemical, Cellular, and Physiological Characterization of Leucettinib-21, a Down Syndrome and Alzheimer’s Disease Drug Candidate

“…A brief bibliographic study of these off-targets suggests that Leucettinibs could be optimized toward some of them and become useful reagents to evaluate and understand their functions or reassigned to new applications. For example, CDKL3 has ciliary and neuronal morphogenesis functions, and its inhibition displays anticancer activities. − CDKL4 also has ciliary function by regulating the ciliary proximal segment length . TAF1L contributes to the development of various cancers. − TRB2 may be involved in Mcl1-dependent apoptosis, macrophage IL-10 production, inflammatory activation of monocytes, and in pro- or anti-cancer regulation. , TRB2 is a pseudokinase that binds ATP and autophosphorylates in a metal-independent manner .…”