ArticleJournal of experimental & clinical cancer research : CR2022
A novel FBW7/NFAT1 axis regulates cancer immunity in sunitinib-resistant renal cancer by inducing PD-L1 expression.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 39 citations in OpenAlex.
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- Immune Escape in Renal Cell Carcinoma: Latest Research and Treatment Strategies.International journal of molecular sciences · 2026Review
- Use of Single-Cell Data and scPagwas Analysis to Identify T Cell Subsets and Construct a Prognostic Model for Clear Cell Renal Cell Carcinoma.Human mutation · 2026Article
- LncRNA TLR8-AS1 Restricts HIV-1 Infection and Inflammation in Macrophages by Suppressing Arachidonic Acid Metabolism Through NFAT1.Journal of inflammation research · 2026Article
- Overexpression of Nuclear Factor of Activated T-cells (NFAT) Transcription Factors Drives Chemoresistance and Poor Outcomes in Pancreatic Cancer.Annals of surgical oncology · 2025Article
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- Unlocking the therapeutic potential of the NFAT pathway in kidney diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- LRRK2 reduces the sensitivity to TKI and PD-1 blockade in ccRCC via activating LPCAT1.Oncogene · 2025Article
- Circulating bile acid profiles characteristics and the potential predictive role in clear cell renal cell carcinoma progression.BMC nephrology · 2025Article
- F-box proteins at the crossroads of ubiquitination and tumor immunity: regulatory networks and immunotherapy strategies.Frontiers in immunology · 2025Review
- Roles of E3 ubiquitin ligases and deubiquitinating enzymes in renal cell carcinoma.Frontiers in oncology · 2025Review
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the "all-around warrior" in immunotherapy.Molecular cancer · 2024Review
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- Disulfidptosis-associated LncRNA signature predicts prognosis and immune response in kidney renal clear cell carcinoma.Biology direct · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Dysregulation of ubiquitination modification in renal cell carcinoma.Frontiers in genetics · 2024Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTyrosine kinase inhibitors (TKIs) alone and in combination with immune checkpoint inhibitors (ICIs) have been shown to be beneficial for the survival of metastatic renal cell carcinoma (mRCC) patients, but resistance to targeted therapy and ICIs is common in the clinic. Understanding the underlying mechanism is critical for further prolonging the survival of renal cancer patients. Nuclear factor of activated T cell 1 (NFAT1) is expressed in immune and nonimmune cells, and the dysregulation of NFAT1 contributes to the progression of various type of malignant tumors. However, the specific role of NFAT1 in RCC is elusive. As a regulator of the immune response, we would like to systemically study the role of NFAT1 in RCC.
methodsTCGA-KIRC dataset analysis, Western blot analysis and RT-qPCR analysis was used to determine the clinic-pathological characteristic of NFAT1 in RCC. CCK-8 assays, colony formation assays and xenograft assays were performed to examine the biological role of NFAT1 in renal cancer cells. RNA-seq analysis was used to examine the pathways changed after NFAT1 silencing. ChIP-qPCR, coimmunoprecipitation analysis, Western blot analysis and RT-qPCR analysis were applied to explore the mechanism by NAFT1 was regulated in the renal cancer cells.
resultsIn our study, we found that NFAT1 was abnormally overexpressed in RCC and that NFAT1 overexpression was associated with an unfavorable prognosis. Then, we showed that NFAT1 enhanced tumor growth and regulated the immune response by increasing PD-L1 expression in RCC. In addition, we demonstrated that NFAT1 was stabilized in sunitinib-resistant RCC via hyperactivation of the PI3K/AKT/GSK-3β signaling pathway. Furthermore, our study indicated that downregulation of the expression of FBW7, which promotes NFAT1 degradation, was induced by FOXA1 and SETD2 in sunitinib-resistant RCC. Finally, FBW7 was found to contribute to modulating the immune response in RCC.
conclusionsOur data reveal a novel role for the FBW7/NFAT1 axis in the RCC response to TKIs and ICIs. NFAT1 and its associated signaling pathway might be therapeutic targets for RCC treatment, especially when combined with ICIs and/or TKIs.
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