ArticleAutophagy2024
Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.
Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- The Diverse Roles of the MEF2 Transcription Factor Family in Tumor Progression and Emerging Therapeutic Opportunities.Biomedicines · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- N-WASP is downregulated in patients with acute myeloid leukemia (AML) and is associated with poor prognosis.Scientific reports · 2026Article
- Role of human Myocyte Enhancer Factor 2 (MEF2) proteins in cancer: structural insights, functional diversity, and regulatory mechanisms.Cancer cell international · 2025Review
- Transcriptional reprogramming in oral squamous cell carcinoma.Scientific reports · 2025Article
- PSMD14 Transcriptionally Activated by MEF2A Promotes Pancreatic Cancer Development by Upregulating SPON2 Expression.The Kaohsiung journal of medical sciences · 2025Article
- Article
- Mechanistic insights into SIRT7 and EZH2 regulation of cisplatin resistance in bladder cancer cells.Cell death & disease · 2024Article
- MEF2A is a transcription factor for circPVT1 and contributes to the malignancy of acute myeloid leukemia.International journal of oncology · 2024Article
- FNIP1 suppresses colorectal cancer progression through inhibiting STAT3 phosphorylation and nuclear translocation.iScience · 2024Article
- HDAC2 promotes autophagy-associated HCC malignant progression by transcriptionally activating LAPTM4B.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) orchestrates diverse environmental signals to facilitate cell growth and is frequently activated in cancer. Translocation of MTORC1 from the cytosol to the lysosomal surface by the RRAG GTPases is the key step in MTORC1 activation. Here, we demonstrated that transcription factors MEF2A and MEF2D synergistically regulated MTORC1 activation via modulating its cyto-lysosome shutting. Mechanically, MEF2A and MEF2D controlled the transcription of FNIP1 and FNIP2, the components of the FLCN-FNIP1 or FNIP2 complex that acts as a RRAGC-RRAGD GTPase-activating element to promote the recruitment of MTORC1 to lysosome and its activation. Furthermore, we determined that the pro-oncogenic protein kinase SRC/c-Src directly phosphorylated MEF2D at three conserved tyrosine residues. The tyrosine phosphorylation enhanced MEF2D transcriptional activity and was indispensable for MTORC1 activation. Finally, both the protein and tyrosine phosphorylation levels of MEF2D are elevated in human pancreatic cancers, positively correlating with MTORC1 activity. Depletion of both MEF2A and MEF2D or expressing the unphosphorylatable MEF2D mutant suppressed tumor cell growth. Thus, our study revealed a transcriptional regulatory mechanism of MTORC1 that promoted cell anabolism and proliferation and uncovered its critical role in pancreatic cancer progression.
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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 Socratic graph.