2. Academic Validation
  3. FAM83A promotes the progression of lung squamous cell carcinoma by inducing the epithelial-mesenchymal transition and inhibiting apoptosis via ERK pathway

FAM83A promotes the progression of lung squamous cell carcinoma by inducing the epithelial-mesenchymal transition and inhibiting apoptosis via ERK pathway

  • Lung Cancer. 2026 Mar:213:108917. doi: 10.1016/j.lungcan.2026.108917.
Xiang Fei 1,  Hao Wu 2,  Mengxing Li 2,  Jianmang Yu 3,  Junyi Huang 4,  Siqi Cao 5,  Shiyou Wei 6,  Qiuyun Wang 7,  Wei Zhu 8,  Zhize Yuan 9
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 2 Department of Clinical Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 3 Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, China; Department of Anesthesiology, Tianmen First People's Hospital, Tianmen, Hubei, China.
  • 4 Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 5 School of Clinical Medicine, Weifang Medical University, Weifang, Shandong, China.
  • 6 Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China; Outcomes Research® Consortium, Houston, TX, USA.
  • 7 Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 8 Department of Radiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: [email protected].
  • 9 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: [email protected].
PMID: 41539215 DOI: 10.1016/j.lungcan.2026.108917
Abstract

Background: The protein Family with Sequence Similarity 83, Member A (FAM83A) is associated with the advancement of various tumors. This study examines the biological function and fundamental processes of FAM83A in lung squamous cell carcinoma (LUSC).

Methods: The GSE33479 dataset was used to compare FAM83A expression levels in LUSC, while the GSE73403 dataset explored its prognostic relevance. FAM83A was knocked down or over-expressed in LUSC cell lines, and CCK-8, colony formation, Transwell, and flow cytometry assays were performed to evaluate the effects of altered FAM83A expression on LUSC cell proliferation, Apoptosis, invasion, and migration. Organoids and animal models were utilized to validate the impact of FAM83A knockdown on tumor growth. Finally, FAM83A-overexpressing LUSC cells were treated with SCH772984, a specific ERK Inhibitor, to elucidate the potential mechanism underlying the oncogenic effect of FAM83A.

Results: FAM83A was upregulated in LUSC tissues and cell lines, with high expression correlating with shorter overall survival. Depletion of FAM83A reduced the migration, invasion, and proliferation of LUSC cells, accompanied by cell cycle arrest and increased apoptotic rate. Western blotting analyses showed that FAM83A knockdown upregulated E-cadherin, Bax, and Cleaved-PARP/Caspase 3, while downregulating N-Cadherin, Vimentin, BCL2, and Cyclin D1. Conversely, overexpression of FAM83A in LUSC cells yielded the opposite phenotypes. In both Organoid cultures and in vivo models, inhibition of FAM83A attenuated tumor growth. Rescue experiments demonstrated that SCH772984 reversed the malignant phenotypes induced by FAM83A over-expression, indicating that FAM83A promoted cell cycle progression, inhibits Apoptosis, and enhances epithelial-mesenchymal transition (EMT) in LUSC through activating the ERK signaling pathway.

Conclusion: FAM83A is crucial in the advancement and spread of LUSC, as it promotes EMT and inhibits Apoptosis via the activation of the ERK pathway. These findings highlight its potential as a strategic molecular target for the treatment of LUSC.

Keywords

Apoptosis; ERK pathway; Epithelial-mesenchymal transition; FAM83A; Lung squamous cell carcinoma.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-50846
    99.83%, ERK1/2 Inhibitor
    ERK