Wu Yueli, Li Hongmei, Wang Hong, Zhang Fenglian, Cao Hua, Xu Shuyun
Department of Obstetrics and Gynecology, Heze Municipal Hospital, Heze, Shandong, China.
Department of Obstetrics and Gynecology, Heze Development Zone Central Hospital, Heze, Shandong, China.
J Cell Biochem. 2019 Jul;120(7):11432-11440. doi: 10.1002/jcb.28421. Epub 2019 Feb 12.
Patients with cervical cancer have abnormal cell proliferation and invasion after many years of latency. However, the precise mechanisms remain unclear. Mitogen- and stress-activated kinase 2 (MSK2) is a serine/threonine kinase which displays a phenotype that promotes tumor growth and metastasis in many different types of tumors. The aim of the present study was to determine the effects of MSK2 on the proliferation of cervical cancer cells and elucidate the signaling pathways through which MSK2 exerts its effects in the pathogenesis of squamous cell carcinoma (SCC). Our results confirmed that MSK2 expression was significantly upregulated in cervical cancer cells both in vivo and in vitro. We further found that the expression patterns of paired-box gene 8 (PAX8) and MSK2 were positively correlated in cervical cancer specimens. Moreover, MSK2 knockdown inhibited the phosphorylation of PAX8 and retinoblastoma protein (RB), and suppressed the sequential expressions of cell proliferation factors E2F1 and cyclin A2, resulting in the inhibition of SCC cell proliferation and tumor formation. Thus, this study demonstrates that MSK2 has oncogenic effects in the formation and development of SCC via the PAX8/RB-E2F1/cyclin A2 axis.
宫颈癌患者在多年潜伏期后会出现异常的细胞增殖和侵袭。然而,确切机制仍不清楚。丝裂原和应激激活激酶2(MSK2)是一种丝氨酸/苏氨酸激酶,在许多不同类型的肿瘤中表现出促进肿瘤生长和转移的表型。本研究的目的是确定MSK2对宫颈癌细胞增殖的影响,并阐明MSK2在鳞状细胞癌(SCC)发病机制中发挥作用的信号通路。我们的结果证实,MSK2在体内和体外的宫颈癌细胞中表达均显著上调。我们进一步发现,配对盒基因8(PAX8)和MSK2的表达模式在宫颈癌标本中呈正相关。此外,MSK2敲低抑制了PAX8和视网膜母细胞瘤蛋白(RB)的磷酸化,并抑制了细胞增殖因子E2F1和细胞周期蛋白A2的顺序表达,从而抑制了SCC细胞增殖和肿瘤形成。因此,本研究表明,MSK2通过PAX8/RB-E2F1/细胞周期蛋白A2轴在SCC的形成和发展中具有致癌作用。