Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1494364
This article is part of the Research Topic Mastering the Dynamics of Tumor Plasticity: Epigenetic Regulation, Cell Fate, and Microenvironment Interactions View all 8 articles

AMBRA1 drives gastric cancer progression through regulation of tumor plasticity

Provisionally accepted
Hai-Jing Zhong Hai-Jing Zhong 1*Liuqi Ye Liuqi Ye 1Danlei Lin Danlei Lin 1Wen Zhang Wen Zhang 1Shiji Chen Shiji Chen 1Yumiao Zhen Yumiao Zhen 1Sara Akkouche Sara Akkouche 1Xiaoxu Liang Xiaoxu Liang 2Cheong-Meng Chong Cheong-Meng Chong 3
  • 1 Jinan University, Guangzhou, China
  • 2 Guangzhou Maritime University, Guangzhou, China
  • 3 University of Macau, Taipa, Macau Region, China

The final, formatted version of the article will be published soon.

    Stomach adenocarcinoma (STAD) is an aggressive malignancy characterized by high tumor plasticity and heterogeneity. This study investigates the role of Autophagy and Beclin 1 Regulator 1 (AMBRA1) in regulating tumor plasticity in STAD progression.Combined with clinical data, the pan-cancer analysis of AMBRA1 was performed to analyze the role of AMBRA1 in STAD. Western blot, Flow Cytometry (FCM) assay, trans-well assay, wound healing assay, MTT, Reactive Oxygen Species (ROS) assay, Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and staining were performed to study the effects of AMBRA1 in AGS human gastric cancer cells. An AGS gastric cancer xenograft model was constructed to further verify the role of AMBRA1 in the development of STAD.AMBRA1 overexpression correlated with poor overall survival in STAD and was positively associated with T cell CD4+ infiltration. High AMBRA1 expression also indicated worse prognosis in patients with high cancer-associated fibroblast infiltration. AMBRA1 depletion suppressed STAD cell proliferation, migration, and invasion in vitro. Mechanistically, AMBRA1 knockdown induced G1/S cell cycle arrest and triggered cellular senescence through epigenetic alterations, including changes in H3K9me3 levels. AMBRA1 inhibition also sensitized STAD cells to chemotherapeutic agents. In vivo studies confirmed the tumor-suppressive effects of AMBRA1 loss, resulting in reduced tumor growth and increased cellular senescence.Our findings uncover an oncogenic role for AMBRA1 in STAD. Targeting AMBRA1 may induce tumor cell senescence, apoptosis, and potentiate anti-tumor immunity, providing a rationale for developing AMBRA1-targeted precision therapies to improve clinical outcomes in STAD patients.

    Keywords: Ambra1, Cell Cycle, senescence, gastric cancer, tumor plasticity

    Received: 10 Sep 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Zhong, Ye, Lin, Zhang, Chen, Zhen, Akkouche, Liang and Chong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hai-Jing Zhong, Jinan University, Guangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.