ArticleProceedings of the National Academy of Sciences of the United States of America2009
Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Identification of EGFR as a Novel Key Gene in Clear Cell Renal Cell Carcinoma (ccRCC) through Bioinformatics Analysis and Meta-Analysis.BioMed research international · 2019Pooled it
- The Hippo pathway in clear cell renal cell carcinoma (ccRCC): a nexus with the VHL disruption?Translational oncology · 2026Review
- Review
- The molecular biology of NF2/Merlin on tumorigenesis and development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Renal Cell Carcinoma of Variant Histology: Biology and Therapies.Hematology/oncology clinics of North America · 2023Review
- MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR.Cancer communications (London, England) · 2023Article
- YAP/TAZ as master regulators in cancer: modulation, function and therapeutic approaches.Nature cancer · 2023Review
- Systemic Therapies for the Management of Non-Clear Cell Renal Cell Carcinoma: What Works, What Doesn't, and What the Future Holds.Clinical genitourinary cancer · 2021Review
- Merlin regulates signaling events at the nexus of development and cancer.Cell communication and signaling : CCS · 2020Review
- Analysis of the role of the Hippo pathway in cancer.Journal of translational medicine · 2019Review
- Deficiency of tumor suppressor Merlin facilitates metabolic adaptation by co-operative engagement of SMAD-Hippo signaling in breast cancer.Carcinogenesis · 2018Article
- G3BP1 promotes tumor progression and metastasis through IL-6/G3BP1/STAT3 signaling axis in renal cell carcinomas.Cell death & disease · 2018Article
- Article
- p120-Catenin is an obligate haploinsufficient tumor suppressor in intestinal neoplasia.The Journal of clinical investigation · 2017Article
- Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets.Nature communications · 2016Article
- Hippo signaling in the kidney: the good and the bad.American journal of physiology. Renal physiology · 2016Review
- Merlin/NF2 Suppresses Pancreatic Tumor Growth and Metastasis by Attenuating the FOXM1-Mediated Wnt/β-Catenin Signaling.Cancer research · 2015Article
- Hippo transducer TAZ promotes epithelial mesenchymal transition and supports pancreatic cancer progression.Oncotarget · 2015Article
- NF2/Merlin mediates contact-dependent inhibition of EGFR mobility and internalization via cortical actomyosin.The Journal of cell biology · 2015Article
- MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The epidermal growth factor receptor (EGFR) has frequently been implicated in hyperproliferative diseases of renal tubule epithelia. We have shown that the NF2 tumor suppressor Merlin inhibits EGFR internalization and signaling in a cell contact-dependent manner. Interestingly, despite the paucity of recurring mutations in human renal cell carcinoma (RCC), homozygous mutation of the NF2 gene is found in approximately 2% of RCC patient samples in the Sanger COSMIC database. To examine the roles of Merlin and EGFR in kidney tumorigenesis, we generated mice with a targeted deletion of Nf2 in the proximal convoluted epithelium using a Villin-Cre transgene. All of these mice developed intratubular neoplasia by 3 months, which progressed to invasive carcinoma by 6-10 months. Kidneys from these mice demonstrated marked hyperproliferation and a concomitant increase in label-retaining putative progenitor cells. Early lumen-filling lesions in this model exhibited hyperactivation of EGFR signaling, altered solubility of adherens junctions components, and loss of epithelial polarity. Renal cortical epithelial cells derived from either early or late lesions were dependent on EGF for in vitro proliferation and were arrested by pharmacologic inhibition of EGFR or re-expression of Nf2. These cells formed malignant tumors upon s.c. injection into immunocompromised mice before in vitro passage. Treatment of Vil-Cre;Nf2(lox/lox) mice with the EGFR inhibitor erlotinib halted the proliferation of tumor cells. These studies give added credence to the role of EGFR signaling and perhaps Nf2 deficiency in RCC and describe a rare and valuable mouse model for exploring the molecular basis of this disease.
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