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Peer-reviewedCC BY-NC-ND 4.0BMC Cancer

SLC3A2 identified as a new therapeutic target for head and neck squamous cell carcinoma

  • Rui Li1
  • Shihui Cao2
  • Xia Liu1
  • Lingkun Zhao2
  • Cheng Gong1
  • Feng Liu3
  • Jingbin Qiu4
  • Chunnuan Wu5
  • Meng Zhao4
  • Jingtao Luo2
5 affiliations
  1. 1Department of Biochemistry and Molecular Biology, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, 300060 China
  2. 2Department of Maxillofacial and Otorhinolaryngological Oncology, Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin, 300060 China
  3. 3Department of Equipment and Materials, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060 China
  4. 4Ali District People’s Hospital, Xizang, 859000 Tibet China
  5. 5Department of Pharmacy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
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Abstract

Background: The head and neck squamous cell carcinomas (HNSCC), which is the most common malignant tumor of head and neck region. Programmed cell death pathways, including the ferroptosis pathway and the disulphide cell apoptotic pathway, have received increasing amounts of attention as potential targets for cancer therapy. However, the features of genes related to disulfidptosis and ferroptosis in HNSCC remain to be investigated.

Methods: We used a random survival forest (RSF) algorithm model, prognostic and immunological effects to screen SLC3A2. Drug sensitivity prediction and single-cell RNA-seq data further confirmed SLC3A2 as a therapeutic target. In addition, we validated SLC3A2 as a therapeutic target for HNSCC through in vitro experiments.

Results: In this study, we used TCGA and GEO database from multiple HNSCC cohorts to identify genes associated with disulphide-related cell death. The prognostic and immunological roles of these genes were investigated, and the key gene related to disulfidoptosis and ferroptosis, SLC3A2, was screened. Drug sensitivity prediction and single-cell RNA-seq data both indicate that SLC3A2 is a potential therapeutic target for the treatment of HNSCC. Furthermore, our experiments suggest that overexpression of SLC3A2 in the absence of glucose suppress growth of HNSCC. We also found that knock down SLC3A2 could induce growth defects. In addition, we treated cells with a RING1B inhibitor to regulate SLC3A2 mRNA expression, identifying it as a potential therapeutic target in HNSCC.

Conclusion: These findings suggested that SLC3A2 is a critical target in HNSCC development, providing new targets and research ideas for the treatment of HNSCC.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16448-7.

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Cite

BibTeXRIS
BibTeX
@article{li2026slc3a2,
  title = {{SLC3A2 identified as a new therapeutic target for head and neck squamous cell carcinoma}},
  author = {Rui Li and Shihui Cao and Xia Liu and Lingkun Zhao and Cheng Gong and Feng Liu and Jingbin Qiu and Chunnuan Wu and Meng Zhao and Jingtao Luo},
  journal = {BMC Cancer},
  year = {2026},
  month = aug,
  doi = {10.1186/s12885-026-16448-7},
  url = {https://doi.org/10.1186/s12885-026-16448-7},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - SLC3A2 identified as a new therapeutic target for head and neck squamous cell carcinoma
AU  - Rui Li
AU  - Shihui Cao
AU  - Xia Liu
AU  - Lingkun Zhao
AU  - Cheng Gong
AU  - Feng Liu
AU  - Jingbin Qiu
AU  - Chunnuan Wu
AU  - Meng Zhao
AU  - Jingtao Luo
PY  - 2026
DA  - 2026/08/11
JO  - BMC Cancer
DO  - 10.1186/s12885-026-16448-7
UR  - https://doi.org/10.1186/s12885-026-16448-7
AB  - Background: The head and neck squamous cell carcinomas (HNSCC), which is the most common malignant tumor of head and neck region. Programmed cell death pathways, including the ferroptosis pathway and the disulphide cell apoptotic pathway, have received increasing amounts of attention as potential targets for cancer therapy. However, the features of genes related to disulfidptosis and ferroptosis in HNSCC remain to be investigated.  Methods: We used a random survival forest (RSF) algorithm model, prognostic and immunological effects to screen SLC3A2. Drug sensitivity prediction and single-cell RNA-seq data further confirmed SLC3A2 as a therapeutic target. In addition, we validated SLC3A2 as a therapeutic target for HNSCC through in vitro experiments.  Results: In this study, we used TCGA and GEO database from multiple HNSCC cohorts to identify genes associated with disulphide-related cell death. The prognostic and immunological roles of these genes were investigated, and the key gene related to disulfidoptosis and ferroptosis, SLC3A2, was screened. Drug sensitivity prediction and single-cell RNA-seq data both indicate that SLC3A2 is a potential therapeutic target for the treatment of HNSCC. Furthermore, our experiments suggest that overexpression of SLC3A2 in the absence of glucose suppress growth of HNSCC. We also found that knock down SLC3A2 could induce growth defects. In addition, we treated cells with a RING1B inhibitor to regulate SLC3A2 mRNA expression, identifying it as a potential therapeutic target in HNSCC.  Conclusion: These findings suggested that SLC3A2 is a critical target in HNSCC development, providing new targets and research ideas for the treatment of HNSCC.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16448-7.
SN  - 1471-2407
ER  -