Zhang Qingyi, Zhao Xuan, Zhang Chaoqi, Wang Wei, Li Feng, Liu Donglei, Wu Kai, Zhu Dengyan, Liu Shasha, Shen Chunyi, Yuan Xin, Zhang Kai, Yang Yang, Zhang Yi, Zhao Song
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan Province 450052, People's Republic of China.
Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China.
Cancer Manag Res. 2019 Aug 19;11:7813-7824. doi: 10.2147/CMAR.S214243. eCollection 2019.
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide and the 5-year overall survival rate remains poor. Protein kinase, membrane associated tyrosine/threonine (PKMYT1) is overexpressed in several cancers and participate in tumor progression. However, the mechanism of PKMYT1 in ESCC is unclear.
The objective of our study was to demonstrate the the expression and role of PKMYT1 in ESCC.
We detected the expression of PKMYT1 in ESCC patients and analysed the correlation with overall survival time and disease-free survival time. Then we detected PKMYT1 expression in ESCC cell lines and immortalized human esophageal epithelial cell line. Down-regulated PKMYT1 was carried out in KYSE70 and KYSE450 cells to invetigate the mechanism of PKMYT1 in ESCC cells.
PKMYT1 was up-regulated in tumor tissues and ESCC cell lines, and higher expression of PKMYT1 correlated with poorer overall survival in ESCC patients. Besides, in ESCC cell lines KYSE70 and KYSE450, knocking down PKMYT1 allowed more cells to skip G2/M checkpoint to complete mitosis, which promoted cell apoptosis, inhibited cell proliferation, and prevented the EMT phenotype in vitro. Meantime, we also observed that down-regulated PKMYT1 in ESCC cells suppressed AKT/mTOR signaling pathway. These results demonstrated PKMYT1 may act as an oncogene in ESCC.
PKMYT1 plays an crutial role in ESCC progression, downregulated PKMYT1 might inhibit the development of ESCC by AKT/mTOR signaling pathway, and might be a novel target in the treatment of ESCC.
食管鳞状细胞癌(ESCC)是全球最常见的恶性肿瘤之一,其5年总生存率仍然很低。膜相关酪氨酸/苏氨酸蛋白激酶(PKMYT1)在多种癌症中过表达并参与肿瘤进展。然而,PKMYT1在ESCC中的作用机制尚不清楚。
本研究旨在证明PKMYT1在ESCC中的表达及作用。
我们检测了ESCC患者中PKMYT1的表达,并分析其与总生存时间和无病生存时间的相关性。然后我们检测了ESCC细胞系和永生化人食管上皮细胞系中PKMYT1的表达。在KYSE70和KYSE450细胞中下调PKMYT1,以研究PKMYT1在ESCC细胞中的作用机制。
PKMYT1在肿瘤组织和ESCC细胞系中上调,且PKMYT1的高表达与ESCC患者较差的总生存率相关。此外,在ESCC细胞系KYSE70和KYSE450中,敲低PKMYT1可使更多细胞跳过G2/M期检查点以完成有丝分裂,从而促进细胞凋亡、抑制细胞增殖并在体外阻止上皮-间质转化(EMT)表型。同时,我们还观察到ESCC细胞中PKMYT1的下调抑制了AKT/mTOR信号通路。这些结果表明PKMYT1可能在ESCC中作为癌基因发挥作用。
PKMYT1在ESCC进展中起关键作用,下调PKMYT1可能通过AKT/mTOR信号通路抑制ESCC的发展,并且可能是ESCC治疗的新靶点。