GTSE1 promotes esophageal squamous cell carcinoma stemness via the Hippo signaling pathway.
5 affiliations
- 1Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
- 2Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
- 3Department of Oncology, Affiliated Gaozhou People's Hospital of Guangdong Medical University, Maoming, China.
- 4Oncology Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
- 5Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat- Sen University Cancer Center, No. 651 Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong, China. [email protected].
Abstract
Background
Cancer stem cells (CSCs) are pivotal in driving tumorigenesis, metastasis, and resistance to multiple drugs. In this study, genes associated with stemness were identified, and the effects of GTSE1 on esophageal squamous cell carcinoma (ESCC) stemness and its underlying mechanism were elucidated.Materials and methods
We utilized a trained stemness index model, adapted from a one-class logistic regression (OCLR) machine-learning approach, to evaluate the stemness indices of ESCC samples based on gene expression-based stemness index (mRNAsi). Subsequent algorithmic and single-cell subtype analyses confirmed the predictive capability of the mRNAsi and pinpointed GTSE1 as a potential target. Loss-of-function and gain-of-function genetic experiments were conducted to evaluate the influence of GTSE1 on ESCC self-renewal and tumor progression. Mechanistic investigations involved RNA sequencing (RNA-seq), immunofluorescence, coimmunoprecipitation (Co-IP) and so on. Additionally, the efficacy of verteporfin (a Hippo pathway inhibitor) was evaluated in vitro and vivo.Results
The analysis of the mRNAsi in bulk RNA-seq and single RNA-seq data reveals elevated expression of GTSE1 in the high mRNAsi subgroup and clusters of highly malignant single cells. Functional studies demonstrate that the depletion of GTSE1 hinders self-renewal and progression of ESCC. Mechanistically, GTSE1 modulates the Hippo signaling pathway. GTSE1 regulates cytoskeletal tension and interacts with LATS1 to facilitate its ubiquitination and degradation, thereby reducing YAP phosphorylation and promoting its nuclear translocation. Treatment with verteporfin, significantly impairs self-renewal and progression, particularly in cells with high GTSE1 expression.Conclusions
This study underscores the association of GTSE1 with the stemness of ESCC, highlighting its interaction with LATS1 to regulate nuclear localization of YAP and modulate the Hippo signaling pathway. Consequently, GTSE1 emerges as a promising therapeutic target for ESCC.
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BibTeX
@article{xie2026gtse1,
title = {{GTSE1 promotes esophageal squamous cell carcinoma stemness via the Hippo signaling pathway.}},
author = {Yujie Xie and Dongmei Lai and Hao Hu and Qinghua Zhou and Xiang Zhang and Yinyin Xue and Bijun Huang},
journal = {Cellular oncology (Dordrecht, Netherlands)},
year = {2026},
month = aug,
doi = {10.1007/s13402-026-01272-9},
url = {https://europepmc.org/article/MED/42972146},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - GTSE1 promotes esophageal squamous cell carcinoma stemness via the Hippo signaling pathway.
AU - Yujie Xie
AU - Dongmei Lai
AU - Hao Hu
AU - Qinghua Zhou
AU - Xiang Zhang
AU - Yinyin Xue
AU - Bijun Huang
PY - 2026
DA - 2026/08/06
JO - Cellular oncology (Dordrecht, Netherlands)
DO - 10.1007/s13402-026-01272-9
UR - https://europepmc.org/article/MED/42972146
AB - Background Cancer stem cells (CSCs) are pivotal in driving tumorigenesis, metastasis, and resistance to multiple drugs. In this study, genes associated with stemness were identified, and the effects of GTSE1 on esophageal squamous cell carcinoma (ESCC) stemness and its underlying mechanism were elucidated.Materials and methods We utilized a trained stemness index model, adapted from a one-class logistic regression (OCLR) machine-learning approach, to evaluate the stemness indices of ESCC samples based on gene expression-based stemness index (mRNAsi). Subsequent algorithmic and single-cell subtype analyses confirmed the predictive capability of the mRNAsi and pinpointed GTSE1 as a potential target. Loss-of-function and gain-of-function genetic experiments were conducted to evaluate the influence of GTSE1 on ESCC self-renewal and tumor progression. Mechanistic investigations involved RNA sequencing (RNA-seq), immunofluorescence, coimmunoprecipitation (Co-IP) and so on. Additionally, the efficacy of verteporfin (a Hippo pathway inhibitor) was evaluated in vitro and vivo.Results The analysis of the mRNAsi in bulk RNA-seq and single RNA-seq data reveals elevated expression of GTSE1 in the high mRNAsi subgroup and clusters of highly malignant single cells. Functional studies demonstrate that the depletion of GTSE1 hinders self-renewal and progression of ESCC. Mechanistically, GTSE1 modulates the Hippo signaling pathway. GTSE1 regulates cytoskeletal tension and interacts with LATS1 to facilitate its ubiquitination and degradation, thereby reducing YAP phosphorylation and promoting its nuclear translocation. Treatment with verteporfin, significantly impairs self-renewal and progression, particularly in cells with high GTSE1 expression.Conclusions This study underscores the association of GTSE1 with the stemness of ESCC, highlighting its interaction with LATS1 to regulate nuclear localization of YAP and modulate the Hippo signaling pathway. Consequently, GTSE1 emerges as a promising therapeutic target for ESCC.
SN - 2211-3428
SN - 2211-3436
ER -