ArticleCancer communications (London, England)2023
MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR.
Article in Cancer communications (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Drug repurposing of ticagrelor suppresses renal cell carcinoma growth by blockading the EGFR/PI3K/AKT axis.Annals of medicine · 2026Article
- Attenuation of EGFR-Mediated Cellular Signaling by Sialidase-Mediated Desialylation.Research square · 2026Article
- Glucocorticoids elevate clear cell renal cell carcinoma sensitivity to HIF-2α inhibitors by suppressing H4K12 lactylation.Signal transduction and targeted therapy · 2026Article
- Mitofusin-2 suppresses tumor immune escape through EGFR/STAT3-mediated PD-L1 transcription.Cell death & disease · 2026Article
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Mechanism ofFrontiers in pharmacology · 2026Article
- High matrix stiffness triggers the YAP-OPA1-TET1/3 loop to drive chemoresistance via enhanced nuclear-mitochondrial communication.iScience · 2025Article
- TWF2 Drives Tumor Progression and Sunitinib Resistance in Renal Cell Carcinoma through Hippo Signaling Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The circRNA-mediated ceRNA molecular regulatory network in fatigue-type type 2 diabete.Journal of translational medicine · 2025Article
- Tumor associated chromosomal instability drives colorectal adenoma to adenocarcinoma progression based on 17 year follow up evidence.Scientific reports · 2025Article
- MANF overexpression ameliorates oxidative stress-induced apoptosis of human nucleus pulposus cells by facilitating mitophagy through promoting MFN2 expression.Scientific reports · 2025Article
- Molecular mechanisms of renal cell carcinoma metastasis and potential targets for therapy.Frontiers in cell and developmental biology · 2025Review
- Exploring necrosis-associated mitochondrial gene signatures: revealing their role in prognosis and immunotherapy of renal clear cell carcinoma.Clinical and experimental medicine · 2024Review
- MFN2 suppresses the accumulation of lipid droplets and the progression of clear cell renal cell carcinoma.Cancer science · 2024Article
- Exosomes from IH- Induced bEnd3 Cells Promote OSA Cognitive Impairment via miR-20a-5p/MFN2 Mediated Pyroptosis of HT22 Cells.Nature and science of sleep · 2024Article
- Circular RNA TAF4B targeting MFN2 accelerates cell growth in bladder cancer through p27 depression and AKT activation.Frontiers in immunology · 2024Article
- MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR.Cancer communications (London, England) · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClear cell renal cell carcinoma (ccRCC) is the most lethal renal cancer. An overwhelming increase of patients experience tumor progression and unfavorable prognosis. However, the molecular events underlying ccRCC tumorigenesis and metastasis remain unclear. Therefore, uncovering the underlying mechanisms will pave the way for developing novel therapeutic targets for ccRCC. In this study, we sought to investigate the role of mitofusin-2 (MFN2) in supressing ccRCC tumorigenesis and metastasis.
methodsThe expression pattern and clinical significance of MFN2 in ccRCC were analyzed by using the Cancer Genome Atlas datasets and samples from our independent ccRCC cohort. Both in vitro and in vivo experiments, including cell proliferation, xenograft mouse models and transgenic mouse model, were used to determine the role of MFN2 in regulating the malignant behaviors of ccRCC. RNA-sequencing, mass spectrum analysis, co-immunoprecipitation, bio-layer interferometry and immunofluorescence were employed to elucidate the molecular mechanisms for the tumor-supressing role of MFN2.
resultswe reported a tumor-suppressing pathway in ccRCC, characterized by mitochondria-dependent inactivation of epidermal growth factor receptor (EGFR) signaling. This process was mediated by the outer mitochondrial membrane (OMM) protein MFN2. MFN2 was down-regulated in ccRCC and associated with favorable prognosis of ccRCC patients. in vivo and in vitro assays demonstrated that MFN2 inhibited ccRCC tumor growth and metastasis by suppressing the EGFR signaling pathway. In a kidney-specific knockout mouse model, loss of MFN2 led to EGFR pathway activation and malignant lesions in kidney. Mechanistically, MFN2 preferably binded small GTPase Rab21 in its GTP-loading form, which was colocalized with endocytosed EGFR in ccRCC cells. Through this EGFR-Rab21-MFN2 interaction, endocytosed EGFR was docked to mitochondria and subsequently dephosphorylated by the OMM-residing tyrosine-protein phosphatase receptor type J (PTPRJ).
conclusionsOur findings uncover an important non-canonical mitochondria-dependent pathway regulating EGFR signaling by the Rab21-MFN2-PTPRJ axis, which contributes to the development of novel therapeutic strategies for ccRCC.
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