ORIGINAL RESEARCH article
Front. Oncol.
Sec. Head and Neck Cancer
This article is part of the Research TopicAdvancements in Personalized Medicine for Head and Neck Cancer: Molecular-based Approaches to Treatment and CareView all 14 articles
Downregulation of HDGF Inhibits Tumorigenic Phenotypes of Hypopharyngeal Squamous Cell Carcinoma by Suppressing the AKT/mTOR/VEGF pathway
Provisionally accepted
- 1School of First Clinical Medicine, Ningxia Medical University, Yinchuan, China
- 2Department of Urology, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
- 3Inner Mongolia Xingan League People's Hospital, Ulanhot, China
- 4Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Hypopharyngeal squamous cell carcinoma (HSCC), an aggressive HNSCC subtype characterized by high metastatic potential and poor prognosis, frequently overexpresses hepatoma-derived growth factor (HDGF), a factor implicated in tumor progression. This study investigates the functional role of HDGF in HSCC and its regulatory mechanisms involving epithelial-mesenchymal transition (EMT) and the AKT/mTOR/VEGF signaling pathway. Methods: Bioinformatic analysis of TCGA data revealed elevated HDGF expression in HSCC tissues, significantly correlating with clinical stage. HDGF expression was depleted in the FaDu HSCC cell line using siRNA. Cell proliferation, migration, and invasion were assessed using CCK-8, wound healing, and Transwell assays, respectively. Western blotting evaluated changes in EMT markers (E-cadherin, N-cadherin, Snail, Slug) and key components of the AKT/mTOR/VEGF pathway (p-AKT, p-mTOR, VEGFA). Results: Bioinformatics analysis confirmed HDGF overexpression across HNSCC subtypes. In FaDu HSCC cells, siRNA-mediated HDGF knockdown significantly attenuated proliferation, migration, and invasion. Mechanistically, HDGF depletion reversed EMT progression, evidenced by E-cadherin upregulation and concurrent N-cadherin, Snail, and Slug downregulation. Western blotting demonstrated that HDGF knockdown suppressed AKT/mTOR signaling, as indicated by reduced p-AKT and p-mTOR levels, and decreased VEGFA expression. Conclusion: Our findings establish HDGF as a key promoter of HSCC progression through dual regulation of EMT and AKT/mTOR/VEGF pathways, suggesting its potential as a therapeutic target. These results provide mechanistic insights for developing HDGF-targeted strategies against this lethal malignancy, warranting further clinical exploration.
Keywords: hdgf, Hypopharyngeal squamous cell carcinoma, tumorigenic phenotypes, AKT-mTOR-VEGF signaling, Epithelial-Mesenchymal Transition
Received: 10 Aug 2025; Accepted: 24 Oct 2025.
Copyright: © 2025 Liu, Zhang, Shan, Du, Han and Yang. 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: Feilong Yang, 904100144@qq.com
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.