The metabolic reprogramming of γ-aminobutyrate in oral squamous cell carcinoma - Research Article

Sep 21, 2026

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, and while oncometabolites have been studied, the mechanism of metabolic reprogramming remains unclear. The study aimed to find metabolic markers distinguishing malignant OSCC tissue from adjacent healthy tissue and to clarify how metabolic reprogramming occurs. Metabolites from cancerous versus paracancerous tissues were compared by 1H NMR; OSCC-derived cells were analyzed by RNA sequencing, real-time PCR, and western blotting, revealing increased γ-aminobutyrate production and a glutamate-glutamine-glutamate cycle–dependent pathway.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

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Abstract

Introduction

Metabolomics in OSCC

Rationale for studying metabolic reprogramming

Wu et al. BMCOral Health (2024) 24:418 [https://doi.org/10.1186/s12903-024-04174-0](https://doi.org/10.1186/s12903-024-04174-0) BMC Oral Health RESEARCH Open Access The metabolic reprogramming of γ-aminobutyrate in oral squamous cell carcinoma Shi-Lian Wu 1, Guang-Yu Zha 1, Ke-Bin Tian 1, Jun Xu 1 and Ming-Guo Cao 1* Abstract Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. The oncometabolites have been studied in OSCC, but the mechanism of metabolic reprogramming remains unclear. To identify the potential metabolic markers to distinguish malignant oral squamous cell carcinoma (OSCC) tissue from adjacent healthy tissue and study the mechanism of metabolic reprogramming in OSCC. We compared the metabolites between cancerous and paracancerous tissues of OSCC patients by 1 HNMR analysis. We established OSCC derived cell lines and analyzed their difference of RNA expression by RNA sequencing. We investigated the metabolism of γ-aminobutyrate in OSCC derived cells by real time PCR and western blotting. Our data revealed that much more γ-aminobutyrate was produced in cancerous tissues of OSCC patients. The investigation based on OSCC derived cells showed that the increase of γ-aminobutyrate was promoted by the synthesis of glutamate beyond the mitochondria. In OSCC cancerous tissue derived cells, the glutamate was catalyzed to glutamine by glutamine synthetase (GLUL), and then the generated glutamine was metabolized to glutamate by glutaminase (GLS) . Finally, the glutamate produced by glutamate-glutamine-glutamate cycle was converted to γ-aminobutyrate by glutamate decarboxylase 2 (GAD2) . Our study is not only benefit for understanding the pathological mechanisms of OSCC, but also has application prospects for the diagnosis of OSCC. Keywords Oral squamous cell carcinoma, Metabolic reprogramming, γ-aminobutyrate Introduction Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, and its incidence has been increasing in several countries [1]. OSCC developsin the oral cavity and oropharynx and can occur due to many etiological factors [2]. Potentially malignant disorders transforming into OSCC includes leukoplakia, proliferative verrucous leukoplakia, erythroleukoplakia, *Correspondence: Ming-Guo Cao [cmg@lsu.edu.cn](cmg@lsu.edu.cn) 1School of Medicine, Lishui University, No 01, Rd Xueyuan Avenue, Lishui 323000, Zhejiang, China erythroplakia, oral submucous fibrosis and oral lichen planus [2]. Gene mutations may cause cancer development in the pharynx and oral cavity; however, no specific gene has been identified in OSCCs [3]. Up-to-date, several molecular markers of prognosis have been studied in OSCC, but none entered in the clinical setting [4]. Because they are overexpressed in OSCC relative to normal mucosa, cytokeratins (CKs) are possibilities for diagnostic markers of OSCC [5]. The expression of CK5/14 and vimentin correlated with a poor prognosis of oral cancer patients [6]. The immunohistochemical detection of CK5/14 and ki-67 was normally performed for the examination of OSCC [7]. © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativec

FAQs

What was the main goal of this OSCC study?

To identify potential metabolic markers distinguishing malignant OSCC tissue from adjacent healthy tissue and to investigate the mechanism behind metabolic reprogramming in OSCC.

How were metabolites compared between cancerous and paracancerous tissues?

Metabolites from cancerous and paracancerous tissues were compared using 1H NMR analysis.

Which pathway promotes increased γ-aminobutyrate production in OSCC?

The increase in γ-aminobutyrate was promoted beyond mitochondria through a glutamate-driven process: glutamate to glutamine via GLUL, glutamine to glutamate via GLS, and then conversion to γ-aminobutyrate by GAD2.

Sep 21, 2026

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