1. Academic Validation
  2. NDRG2 suppresses proliferation, migration, invasion and epithelial-mesenchymal transition of esophageal cancer cells through regulating the AKT/XIAP signaling pathway

NDRG2 suppresses proliferation, migration, invasion and epithelial-mesenchymal transition of esophageal cancer cells through regulating the AKT/XIAP signaling pathway

  • Int J Biochem Cell Biol. 2018 Jun;99:43-51. doi: 10.1016/j.biocel.2018.03.003.
Cheng-Liang Yang 1 Xiao-Li Zheng 2 Ke Ye 2 Hong Ge 2 Ya-Nan Sun 2 Yu-Fei Lu 2 Qing-Xia Fan 3
Affiliations

Affiliations

  • 1 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China; Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, PR China.
  • 2 Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, PR China.
  • 3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China. Electronic address: [email protected].
Abstract

N-Myc downstream-regulated gene 2 (NDRG2) has recently revealed as a candidate tumor suppressor gene. To inhibit tumor growth and decrease morbidity of esophageal Cancer (EC), this study aims to test the hypothesis that the upregulation of NDRG2 may suppress proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of EC cells by regulating the Akt/XIAP signaling pathway. Immunohistochemistry was conducted for the identification of NDRG2, protein kinase B (p-AKT), X-linked inhibitor of Apoptosis protein (XIAP) in EC tissues. To identify the regulatory mechanism of NDRG2 on the Akt/XIAP signaling pathway and EMT in EC, over-expressed lentiviral vector and shRNA were applied for up-regulating and interfering NDRG2 expression, and a series of determinations on the biological behavior of EC cells were performed to validate this regulation action. The results of immunohistochemistry showed NDRG2 was lowly expressed in EC tissues while p-AKT and XIAP are highly expressed. Over-expression of NDRG2 suppresses the proteins related to Akt/XIAP signaling pathway and EMT. Besides, a series of determinations shows the proliferation, migration and invasion of TE-13 cells were suppressed by over-expressed NDRG2, while the cell cycle progression was blocked and cell Apoptosis was promoted. And in vivo experiment also demonstrated NDRG2 could inhibit tumor growth. Our findings demonstrate over-expression of NDRG2 works as tumor suppressive role in EC through its effects on inhibition of cell migration, invasion, and EMT by inhibiting the Akt/XIAP signaling pathway.

Keywords

AKT/XIAP signaling pathway; Epithelial-mesenchymal transition; Esophageal cancer; Invasion; Migration; NDRG2; Proliferation.

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