ArticleProceedings of the National Academy of Sciences of the United States of America2011
Chromosomal amplification of leucine-rich repeat kinase-2 (LRRK2) is required for oncogenic MET signaling in papillary renal and thyroid carcinomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 93 citations in OpenAlex.
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Review
- Hydroxytyrosol has a protective effect on the kidneys through dardarin and spexin.Northern clinics of Istanbul · 2025Article
- Article
- Dysregulated LINC01133 expression in laryngeal carcinoma: Prognostic implications and predicted ceRNA interactome.Molecular biology research communications · 2025Article
- Candidate biomarkers for treatment benefit from sunitinib in patients with advanced renal cell carcinoma using mass spectrometry-based (phospho)proteomics.Clinical proteomics · 2023Article
- Targeting leucine-rich repeat serine/threonine-protein kinase 2 sensitizes pancreatic ductal adenocarcinoma to anti-PD-L1 immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Differential Activation of NRF2 Signaling Pathway in Renal-Cell Carcinoma Caki Cell Lines.Biomedicines · 2023Article
- Genetic correlation between thyroid hormones and Parkinson's disease.Clinical and experimental immunology · 2022Article
- Dissection of PD-L1 promoter reveals differential transcriptional regulation of PD-L1 in VHL mutant clear cell renal cell carcinoma.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Current progress, challenges and future prospects of indazoles as protein kinase inhibitors for the treatment of cancer.RSC advances · 2021Review
- LRRK2 is a candidate prognostic biomarker for clear cell renal cell carcinoma.Cancer cell international · 2021Article
- Three-dimensional coculture provides an improved in vitro model for papillary renal cell carcinoma.American journal of physiology. Renal physiology · 2021Article
- Article
- TM4SF4 and LRRK2 Are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis.Cancer research and treatment · 2021Article
- Shedding light on thyroid hormone disorders and Parkinson disease pathology: mechanisms and risk factors.Journal of endocrinological investigation · 2021Review
- Article
- Co-Regulation of Immune Checkpoint PD-L1 with Interferon-Gamma Signaling is Associated with a Survival Benefit in Renal Cell Cancer.Targeted oncology · 2020Article
- Identification of hub driving genes and regulators of lung adenocarcinoma based on the gene Co-expression network.Bioscience reports · 2020Article
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
The receptor tyrosine kinase MET is frequently amplified in human tumors, resulting in high cell surface densities and constitutive activation even in the absence of growth factor stimulation by its endogenous ligand, hepatocyte growth factor (HGF). We sought to identify mechanisms of signaling crosstalk that promote MET activation by searching for kinases that are coordinately dysregulated with wild-type MET in human tumors. Our bioinformatic analysis identified leucine-rich repeat kinase-2 (LRRK2), which is amplified and overexpressed in papillary renal and thyroid carcinomas. Down-regulation of LRRK2 in cultured tumor cells compromises MET activation and selectively reduces downstream MET signaling to mTOR and STAT3. Loss of these critical mitogenic pathways induces cell cycle arrest and cell death due to loss of ATP production, indicating that MET and LRRK2 cooperate to promote efficient tumor cell growth and survival in these cancers.
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