Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 4: 404 - 414

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.04.002

Basic research

Mechanism of Fas-associated protein with death domain in promoting proliferation of head and neck squamous cell carcinoma cells

  • CHEN Yinan ,
  • ZHENG Yang ,
  • ZENG Hanlin ,
  • LEI Ming
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  • 1.Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China
    2.Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China
    3.Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, China
LEI Ming, E-mail: leim@shsmu.edu.cn.

Received date: 2024-08-16

  Accepted date: 2024-12-09

  Online published: 2025-04-28

Supported by

The National Natural Science Foundation of China(82204421)

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Abstract

Objective ·To detect the expression level of Fas-associated protein with death domain (FADD) in head and neck squamous cell carcinoma (HNSCC) and to explore the molecular mechanisms by which FADD promotes the proliferation of HNSCC cells. Methods ·The GEPIA 2 database was utilized to analyze the expression level of FADD in tumor tissues and to evaluate its association with prognosis. Immunohistochemistry staining (IHC) was performed on HNSCC tissues to investigate the changes in FADDexpression levels in normal, dysplastic, and tumor tissues. Stable FADD-knockdown Fadu and HSC3 cell lines were constructed and validated using Western blotting and quantitative real-time PCR (qRT-PCR). The regulatory effect of FADD on the proliferation of HNSCC cells was explored using the LiveCyte live-cell tracking system, colony formation assay, and cell viability assay. Proteins interacting with FADD were identified by co-immunoprecipitation mass spectrometry (Co-IP/MS), and further mechanistic studies were conducted using CRISPR/Cas9 technology, LiveCyte live-cell tracking system, and Western blotting. Results ·Analysis of the GEPIA2 database indicated that FADD was significantly overexpressed in head and neck cancer and was associated with poor prognosis. IHC staining showed that FADD expression levels progressively increased from normal to dysplastic to tumor tissues in HNSCC patients. Knockdown of FADD in HNSCC cells resulted in significantly reduced proliferation and colony formation compared to the control group. Co-IP/MS results showed that FADD interacted with the CUX1 protein, and FADD knockdown led to increased CUX1 expression. Moreover, CUX1 knockdown significantly promoted HNSCC cell proliferation and reversed the anti-proliferative phenotype caused by FADD knockdown. Conclusion ·FADD plays a significant pro-carcinogenic role in HNSCC and is associated with poor prognosis. FADD can further regulate tumor cell proliferation by interacting with CUX1 and suppressing its expression level.

Key words： Fas-associated protein with death domain (FADD); CUT-like homeobox 1 (CUX1); head and neck squamous cell carcinoma (HNSCC); cell proliferation

Cite this article

CHEN Yinan , ZHENG Yang , ZENG Hanlin , LEI Ming . Mechanism of Fas-associated protein with death domain in promoting proliferation of head and neck squamous cell carcinoma cells[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(4) : 404 -414 . DOI: 10.3969/j.issn.1674-8115.2025.04.002

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