ArticleSignal transduction and targeted therapy
Targeting the insulin-like growth factor-1 receptor in MTAP-deficient renal cell carcinoma.
Article in Signal transduction and targeted therapy. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Comprehensive Genomic and Transcriptomic Characterization of MTAP Loss across Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Observational
- Immunohistochemical Loss of MTAP as a Diagnostic and Prognostic Surrogate ofDiagnostics (Basel, Switzerland) · 2026Review
- Single-cell profiling of bone metastasis ecosystems reveals pivotal role of INSRTranslational oncology · 2026Article
- Machine learning-derived prognostic signature integrating programmed cell death and mitochondrial function in renal clear cell carcinoma: identification of PIF1 as a novel target.Cancer immunology, immunotherapy : CII · 2025Article
- Emerging roles for methionine metabolism in immune cell fate and function.Frontiers in immunology · 2025Review
- Immune suppression in MTAP-deficient cancers via glutamate metabolism and CXCL10 downregulation.Frontiers in immunology · 2025Article
- Exosome-related lncRNA score: A value-based individual treatment strategy for predicting the response to immunotherapy in clear cell renal cell carcinoma.Cancer medicine · 2024Article
- Disulfidptosis status influences prognosis and therapeutic response in clear cell renal cell carcinoma.Aging · 2024Article
- Enzyme-mediated depletion of methylthioadenosine restores T cell function in MTAP-deficient tumors and reverses immunotherapy resistance.Cancer cell · 2023Article
- Article
- Deciphering key genes involved in cisplatin resistance in kidney renal clear cell carcinoma through a combinedOncology research · 2023Article
- Reduced symmetric dimethylation stabilizes vimentin and promotes metastasis in MTAP-deficient lung cancer.EMBO reports · 2022Article
- From Basic Science to Clinical Translation in Kidney Cancer: A Report from the Second Kidney Cancer Research Summit.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Integrative Analysis of the Genomic and Immune Microenvironment Characteristics Associated With Clear Cell Renal Cell Carcinoma Progression: Implications for Prognosis and Immunotherapy.Frontiers in immunology · 2022Article
- A Novel Renoprotective Strategy: Upregulation of PD-L1 Mitigates Cisplatin-Induced Acute Kidney Injury.International journal of molecular sciences · 2021Article
- Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine.Nature communications · 2021Article
- IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R.Cell death & disease · 2021Article
- Lung cancer‑associated transcript 1 facilitates tumorigenesis in laryngeal squamous cell carcinoma through the targeted inhibition of miR‑493.Molecular medicine reports · 2021Article
- The Heterogeneity Metabolism of Renal Cell Carcinomas.Advances in experimental medicine and biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Renal cell carcinoma (RCC) has emerged as a metabolic disease characterized by dysregulated expression of metabolic enzymes. Patients with metastatic RCC have an unusually poor prognosis and near-universal resistance to all current therapies. To improve RCC treatment and the survival rate of patients with RCC, there is an urgent need to reveal the mechanisms by which metabolic reprogramming regulates aberrant signaling and oncogenic progression. Through an integrated analysis of RCC metabolic pathways, we showed that methylthioadenosine phosphorylase (MTAP) and its substrate methylthioadenosine (MTA) are dysregulated in aggressive RCC. A decrease in MTAP expression was observed in RCC tissues and correlated with higher tumor grade and shorter overall survival. Genetic manipulation of MTAP demonstrated that MTAP expression inhibits the epithelial-mesenchymal transition, invasion and migration of RCC cells. Interestingly, we found a decrease in the protein methylation level with a concomitant increase in tyrosine phosphorylation after MTAP knockout. A phospho-kinase array screen identified the type 1 insulin-like growth factor-1 receptor (IGF1R) as the candidate with the highest upregulation in tyrosine phosphorylation in response to MTAP loss. We further demonstrated that IGF1R phosphorylation acts upstream of Src and STAT3 signaling in MTAP-knockout RCC cells. IGF1R suppression by a selective inhibitor of IGF1R, linsitinib, impaired the cell migration and invasion capability of MTAP-deleted cells. Surprisingly, an increase in linsitinib-mediated cytotoxicity occurred in RCC cells with MTAP deficiency. Our data suggest that IGF1R signaling is a driver pathway that contributes to the aggressive nature of MTAP-deleted RCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.