ArticleOncogene2020
VHL-HIF-2α axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Genetic landscape and functional exploration of kidney cancer predisposition in cross-ancestral populations.Nature communications · 2026Pooled it
- The gradual expansion of multiple intramedullary metastatic renal cell carcinoma in a patient with von Hippel-Lindau disease with multiple intramedullary hemangioblastomas: illustrative case.Journal of neurosurgery. Case lessons · 2025Article
- SMYD3 Promotes Immune Evasion in Clear Cell Renal Cell Carcinoma via SREBP1-Mediated Transactivation of CD47.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- SMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance.Experimental & molecular medicine · 2024Review
- SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair.Oncogenesis · 2024Article
- Identification of key genes and signalling pathways in clear cell renal cell carcinoma: An integrated bioinformatics approach.Cancer biomarkers : section A of Disease markers · 2024Article
- Candidate biomarkers for treatment benefit from sunitinib in patients with advanced renal cell carcinoma using mass spectrometry-based (phospho)proteomics.Clinical proteomics · 2023Article
- MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR.Cancer communications (London, England) · 2023Article
- GABPA-activated TGFBR2 transcription inhibits aggressiveness but is epigenetically erased by oncometabolites in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma.Frontiers in oncology · 2022Article
- The Role of ERBB Signaling Pathway-Related Genes in Kidney Renal Clear Cell Carcinoma and Establishing a Prognostic Risk Assessment Model for Patients.Frontiers in genetics · 2022Article
- ARL4C Regulates the Progression of Clear Cell Renal Cell Carcinoma by Affecting the Wnt/Journal of oncology · 2022Article
- Article
- Loss of Von Hippel-Lindau (International journal of molecular sciences · 2021Review
- LRRK2 is a candidate prognostic biomarker for clear cell renal cell carcinoma.Cancer cell international · 2021Article
- Identifying modules of cooperating cancer drivers.Molecular systems biology · 2021Article
- The crosstalk between HIFs and mitochondrial dysfunctions in cancer development.Cell death & disease · 2021Review
- Huaier Extract Inhibits Prostate Cancer GrowthFrontiers in oncology · 2021Article
- Seven Novel Genes Related to Cell Proliferation and Migration of VHL-Mutated Pheochromocytoma.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.
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