CDKL3 promotes osteosarcoma progression by activating Akt/PKB
CDKL3 promotes osteosarcoma progression by activating Akt/PKB
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CDKL3 通过激活 Akt/PKB 促进骨肉瘤进展
DOI：
10.26508/lsa.202000648
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发表时间：
2020-05-01
影响因子：
4.4
通讯作者：
Xiang, Dongxi
中科院分区：
文献类型：
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作者：
He, Aina;Ma, Lanjing;Xiang, Dongxi
本研究表明，CDKL3调节Akt激活及其下游靶点，促进OS进展，在治疗OS中形成可靶向的治疗漏洞。骨肉瘤（Osteosarcoma， OS）是一种肿瘤转移和复发频率高的原发性骨恶性肿瘤。尽管已知Akt/PKB信号通路在肿瘤发生中起关键作用，但周期蛋白依赖性激酶样3 （CDKL3）在OS进展中的作用仍然难以捉摸。我们已经证明了CDKL3在OS人类标本中的高表达水平，并全面研究了CDKL3在体外和体内促进OS进展中的作用。我们发现CDKL3调节Akt激活及其下游效应，包括细胞生长和自噬。OS标本中CDKL3的上调似乎与Akt激活和较短的患者总生存期相关（P = 0.003）。我们的研究结果表明，CDKL3是通过增强Akt激活来刺激OS进展的关键调节因子。CDKL3既是OS预后的生物标志物，也是精准医学中靶向CDKL3治疗Akt超激活OS的潜在治疗靶点。
This study demonstrates that CDKL3 regulates Akt activation and its downstream targets to promote OS progression, creating a therapeutically targetable vulnerability in treatment of OS. Osteosarcoma (OS) is a primary malignant bone neoplasm with high frequencies of tumor metastasis and recurrence. Although the Akt/PKB signaling pathway is known to play key roles in tumorigenesis, the roles of cyclin-dependent kinase–like 3 (CDKL3) in OS progression remain largely elusive. We have demonstrated the high expression levels of CDKL3 in OS human specimens and comprehensively investigated the role of CDKL3 in promoting OS progression both in vitro and in vivo. We found that CDKL3 regulates Akt activation and its downstream effects, including cell growth and autophagy. The up-regulation of CDKL3 in OS specimens appeared to be associated with Akt activation and shorter overall patient survival (P = 0.003). Our findings identify CDKL3 as a critical regulator that stimulates OS progression by enhancing Akt activation. CDKL3 represents both a biomarker for OS prognosis, and a potential therapeutic target in precision medicine by targeting CDKL3 to treat Akt hyper-activated OS.