ArticlePloS one2010
Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 181 citations in OpenAlex.
- Aggressive high-grade papillary-patterned renal cell carcinomas harboring FLCN mutations: expanding the clinicopathological spectrum in Birt-Hogg-Dubé syndrome and sporadic cases.Virchows Archiv : an international journal of pathology · 2026Article
- GPNMB-directed CAR T cell therapy against MiT/TFE-family fusion-driven solid tumors.Nature cancer · 2026Article
- Diagnostic utility of novel marker TRIM63 ISH in the workup of uterine perivascular epithelioid cell tumors.Virchows Archiv : an international journal of pathology · 2026Article
- Parotid Oncocytomas Express the Glycoprotein Non-metastatic Melanoma Protein B (GPNMB): A Potential Link with Birt-Hogg-Dubé Syndrome.Head and neck pathology · 2026Article
- Review
- FLCN-mutated eosinophilic renal tumors: clinicopathologic and molecular analysis of five cases highlighting morphologic heterogeneity.Virchows Archiv : an international journal of pathology · 2026Article
- FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer.Autophagy reports · 2026Article
- Folliculin Deletion in the Mouse Kidney Results in Cystogenesis of the Loops of Henle via Aberrant TFEB Activation.The American journal of pathology · 2025Article
- Folliculin depletion results in liver cell damage and cholangiocarcinoma through MiT/TFE activation.Cell death and differentiation · 2025Article
- Differential Diagnosis and a Novel Mutation in Birt-Hogg-Dubé Syndrome: Insights from 2 Cases.The American journal of case reports · 2025Article
- TFE3 fusion oncoprotein condensates drive transcriptional reprogramming and cancer progression in translocation renal cell carcinoma.Cell reports · 2025Article
- A novel multigene panel (Sig27) robustly predicts poor prognosis of renal cell carcinoma via high-level associations with immunosuppressive features.BJC reports · 2025Article
- A novel uORF regulates folliculin to promote cell growth and lysosomal biogenesis during cardiac stress.Scientific reports · 2025Article
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- Review
- The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs.Molecular cell · 2024Article
- The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease.Nature reviews. Molecular cell biology · 2023Review
- Article
- The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- TFEB and TFE3 drive kidney cystogenesis and tumorigenesis.EMBO molecular medicine · 2023Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGermline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC) in Birt-Hogg-Dubé syndrome. TFE3 is a member of the MiTF/TFE transcription factor family and Xp11.2 translocations found in sporadic RCC involving TFE3 result in gene fusions and overexpression of chimeric fusion proteins that retain the C-terminal DNA binding domain of TFE3. We found that GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, we hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN. METHODOLOGY/PRINCIPAL
findingsTFE3 knockdown reduced GPNMB expression in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Moreover, FLCN knockdown induced GPNMB expression in FLCN-restored renal cancer cells. Conversely, wildtype FLCN suppressed GPNMB expression in FLCN-null cells. FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization as revealed by elevated GPNMB mRNA and protein expression, and predominantly nuclear immunostaining of TFE3 in renal cancer cells, mouse embryo fibroblast cells, mouse kidneys and mouse and human renal tumors. Nuclear localization of TFE3 was associated with TFE3 post-translational modifications including decreased phosphorylation. CONCLUSIONS/SIGNIFICANCE: Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. This study provides an important novel mechanism for induction of TFE3 activity in addition to TFE3 overexpression resulting from Xp11.2 translocations, suggesting that TFE3 may be more broadly involved in tumorigenesis.
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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.