Cancer Management and Research (Aug 2019)

Overexpressed PKMYT1 promotes tumor progression and associates with poor survival in esophageal squamous cell carcinoma

  • Zhang Q,
  • Zhao X,
  • Zhang C,
  • Wang W,
  • Li F,
  • Liu D,
  • Wu K,
  • Zhu D,
  • Liu S,
  • Shen C,
  • Yuan X,
  • Zhang K,
  • Yang Y,
  • Zhang Y,
  • Zhao S

Journal volume & issue
Vol. Volume 11
pp. 7813 – 7824

Abstract

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Qingyi Zhang,1,* Xuan Zhao,2,* Chaoqi Zhang,3 Wei Wang,4 Feng Li,5 Donglei Liu,1 Kai Wu,1 Dengyan Zhu,1 Shasha Liu,2 Chunyi Shen,2 Xin Yuan,6 Kai Zhang,2 Yang Yang,1 Yi Zhang,2 Song Zhao1,71Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan Province 450052, People’s Republic of China; 2Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of China; 3Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 4Henan Medical Association, Zhengzhou, Henan Province 450000, People’s Republic of China; 5Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Berlin 10117, Germany; 6Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Henan Province 450052, People’s Republic of China; 7Key Laboratory of Thoracic Tumor of Zhengzhou City, Zhengzhou, Henan 450052, People’s Republic of ChinaCorrespondence: Song ZhaoDepartment of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan province 450052, People’s Republic of ChinaTel +86 1 367 366 5008Email [email protected] ZhangBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of ChinaTel +86 1 513 892 8971Email [email protected]*These authors contributed equally to this workBackground: 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.Purpose: The objective of our study was to demonstrate the the expression and role of PKMYT1 in ESCC.Patients and methods:  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.Results: 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.Conclusion: 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.Keywords: ESCC, PKMYT1, AKT, EMT, cell apoptosis

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