ArticleJCI insight2020
ELA/APELA precursor cleaved by furin displays tumor suppressor function in renal cell carcinoma through mTORC1 activation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Role and therapeutic potential of elabela in renal disease: from molecular mechanisms to clinical applications.Endocrine connections · 2025Review
- Microproteins in Metabolism.Cells · 2025Review
- Optimal Stapling of a Helical Peptide-Foldamer Hybrid Using a C-Terminal 4-Mercaptoproline Enhances Protein Surface Recognition and Cellular Activity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.Clinical science (London, England : 1979) · 2025Review
- Apela promotes blood vessel regeneration and remodeling in zebrafish.Scientific reports · 2024Article
- Targeting the apelin system for the treatment of cardiovascular diseases.Cardiovascular research · 2023Review
- Inhibition of the membrane repair protein annexin-A2 prevents tumor invasion and metastasis.Cellular and molecular life sciences : CMLS · 2023Article
- Review
- Elabela blunts doxorubicin-induced oxidative stress and ferroptosis in rat aortic adventitial fibroblasts by activating the KLF15/GPX4 signaling.Cell stress & chaperones · 2023Article
- Advances in the study of ELABELA in renal physiological functions and related diseases.Frontiers in pharmacology · 2023Review
- The nuclear factor of activated T cells 5 (NFAT5) contributes to the renal corticomedullary differences in gene expression.Scientific reports · 2022Article
- On Methods for the Measurement of the Apelin Receptor Ligand Apelin.Scientific reports · 2022Article
- The network map of Elabela signaling pathway in physiological and pathological conditions.Journal of cell communication and signaling · 2022Article
- Article
- Review
- The therapeutic potential of apelin in kidney disease.Nature reviews. Nephrology · 2021Review
- Article
- Furin Prodomain ppFurin Enhances CaCancers · 2021Article
- Study Progression of Apelin/APJ Signaling and Apela in Different Types of Cancer.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apelin is a well-established mediator of survival and mitogenic signaling through the apelin receptor (Aplnr) and has been implicated in various cancers; however, little is known regarding Elabela (ELA/APELA) signaling, also mediated by Aplnr, and its role and the role of the conversion of its precursor proELA into mature ELA in cancer are unknown. Here, we identified a function of mTORC1 signaling as an essential mediator of ELA that repressed kidney tumor cell growth, migration, and survival. Moreover, sunitinib and ELA showed a synergistic effect in repressing tumor growth and angiogenesis in mice. The use of site-directed mutagenesis and pharmacological experiments provided evidence that the alteration of the cleavage site of proELA by furin induced improved ELA antitumorigenic activity. Finally, a cohort of tumors and public data sets revealed that ELA was only repressed in the main human kidney cancer subtypes, namely clear cell, papillary, and chromophobe renal cell carcinoma. Aplnr was expressed by various kidney cells, whereas ELA was generally expressed by epithelial cells. Collectively, these results showed the tumor-suppressive role of mTORC1 signaling mediated by ELA and established the potential use of ELA or derivatives in kidney cancer treatment.
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