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  2. G2 and S phase-expressed-1 induces chromosomal instability in esophageal squamous cell carcinoma cells and inhibits cell apoptosis through ROS/JNK signaling

G2 and S phase-expressed-1 induces chromosomal instability in esophageal squamous cell carcinoma cells and inhibits cell apoptosis through ROS/JNK signaling

  • Mol Carcinog. 2022 Oct 4. doi: 10.1002/mc.23470.
Man Zhang 1 Xianzeng Wang 2 Cong Liu 1 Zhaoyang Zheng 3 Junhu Wan 1 Ying Yang 1 Shuangshuang Chen 3 Hongchun Liu 1
Affiliations

Affiliations

  • 1 Key Clinical Laboratory of Henan Province, Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 2 Department of Thoraric Surgery, Linzhou People's Hospital, Linzhou, China.
  • 3 Department of Medical Laboratory, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Abstract

New diagnostic and therapeutic strategies are urgently needed to improve the prognosis of patients with esophageal squamous cell carcinoma (ESCC), which has high morbidity and mortality. Bioinformatics analysis revealed that cell cycle regulation related molecular G2 and S phase-expressed-1 (GTSE1) was dysregulated in ESCC. In this study, the ectopic expression of GTSE1 was verified in ESCC patients' tissues and cell lines. After overexpression or knockdown of GTSE1 using lentiviral transfection, the effects of GTSE1 on the proliferation, migration, invasion, and Apoptosis of ESCC cells were detected. The contribution of GTSE1 in inducing chromosomal missegregation in cells leading to chromosome instability (CIN) has been described. Long-term existence of CIN can increase Reactive Oxygen Species (ROS) generation in ESCC cells, followed by inhibition of Apoptosis by activating the c-Jun N-terminal kinase (JNK) signaling pathway, and this inhibition could be relieved after treatment with JNK Inhibitor. In vivo experiments, we also confirmed the tumor-promoting effect and mechanism of GTSE1 in ESCC using nude mice model. In this study, we demonstrated that GTSE1 induces CIN in ESCC cells, and increases intracellular ROS production, which leads to cellular oxidative stress, contributes to the activation of the JNK signaling pathway, and thereby inhibits Apoptosis leading to ESCC tumorigenesis.

Keywords

ESCC; GTSE1; JNK signaling pathway; ROS; cell apoptosis; chromosomal instability.

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