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

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.

GTSE1: A potential prognostic and diagnostic biomarker in various tumors including lung adenocarcinoma

“…Up to now, numerous studies have demonstrated that GTSE1 is a potential risk gene for the development and progression of different tumors, including prostate cancer, BRCA, liver cancer, and others. 13 , 15 , 26 Overexpression of GTSE1 has been found to inhibit apoptosis in esophageal malignant tumor cells 16 and promote the growth and metastasis of LUAD cells. 17 Despite the extensive research on pan‐cancer in the past 5 years, the association between GTSE1 and various malignant tumors remains unexplored.…”

“… 11 GTSE1 has been implicated in various malignant tumors, including osteosarcoma, BRCA, and colon cancer, regarding their occurrence, development, and prognosis. 12 , 13 , 14 Lai et al 15 found that upregulation of GTSE1 can stimulate the growth of prostate cancer cells via the SP1/FOXM1 signaling pathway, while Zhang et al 16 suggested that GTSE1 induces chromosomal instability in esophageal squamous cell carcinoma cells and inhibits cell apoptosis through the ROS/JNK signaling pathway. Furthermore, enhancing GTSE1 expression facilitates the growth and spread of LUAD cells through the activation of alternative signaling pathways, such as the AKT/mTOR and ERK/MAPK pathways.…”

Systematical identification of key genes and regulatory genetic variants associated with prognosis of esophageal squamous cell carcinoma

“…With the continuous development and wide application of highthroughput sequencing and microarray technology, researchers have carried out many studies on the association between gene expression and the prognosis of ESCC. [12][13][14][15][16][17][18] However, the results of many studies are not completely consistent due to the limited sample size and study design. Genome-wide association studies (GWAS) have found many prognostic genetic variants in various cancer prognostic studies, [19][20][21][22][23] suggesting that genetic variants as regulatory molecules of gene expression may be potential prognostic markers for cancer.…”

“…With the continuous development and wide application of high‐throughput sequencing and microarray technology, researchers have carried out many studies on the association between gene expression and the prognosis of ESCC 12–18 . However, the results of many studies are not completely consistent due to the limited sample size and study design.…”

GTSE1 promotes nasopharyngeal carcinoma proliferation and angiogenesis by upregulating STMN1

“…The role of GTSE1 in drug resistance is shown in gastric cancer cells [ 24 ], osteosarcoma [ 25 ], breast cancer [ 23 ], clear cell renal cell carcinoma [ 19 ], and non-small-cell lung cancer [ 26 ]. In addition, GTSE1 is demonstrated to be involved in apoptosis in clear cell renal cell carcinoma [ 20 ], gastric cancer cells [ 24 ] and esophageal squamous cell carcinoma [ 27 ], and it was also involved in Warburg effect in cervical cancer [ 28 ].Furthermore, GTSE1 has been identified to be upregulated in head and neck squamous cell carcinoma (HNSC) [ 13 ], and GTSE1 can act as one of nine genes contributing to build the model for the prognostic risk prediction of HNSC [ 29 ], which indicated that GTSE1 might be involved in the progression of NPC.…”