ArticleProceedings of the National Academy of Sciences of the United States of America2020
Splice variant of growth hormone-releasing hormone receptor drives esophageal squamous cell carcinoma conferring a therapeutic target.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Phosphofructokinase-1 redefined: a metabolic hub orchestrating cancer hallmarks through multi-dimensional control networks.Journal of translational medicine · 2025Review
- PFKM phosphorylates histone H3 and promotes mitotic progression by sensing the levels of citrate.Nature communications · 2025Article
- Growth hormone-releasing hormone and cancer.Reviews in endocrine & metabolic disorders · 2025Review
- Effects of GHRH and its analogues on the Vascular System.Reviews in endocrine & metabolic disorders · 2025Review
- Update on regulation of GHRH and its actions on GH secretion in health and disease.Reviews in endocrine & metabolic disorders · 2025Review
- The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders.Reviews in endocrine & metabolic disorders · 2025Review
- Review
- Growth Hormone-Releasing Hormone Antagonists Increase Radiosensitivity in Non-Small Cell Lung Cancer Cells.International journal of molecular sciences · 2025Article
- Growth hormone-releasing hormone and its analogues in health and disease.Nature reviews. Endocrinology · 2025Review
- A CDKN2B-Associated Immune Prognostic Model for Predicting Immune Cell Infiltration and Prognosis in Esophageal Carcinoma.Clinical and experimental gastroenterology · 2025Article
- Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma.Frontiers of medicine · 2024Article
- Identification of Small-Molecule Antagonists Targeting the Growth Hormone Releasing Hormone Receptor (GHRHR).Journal of chemical information and modeling · 2024Article
- Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in a Cohort of Hungarian Pediatric Patients with Hematological and Oncological Disorders: A Pilot Study.International journal of molecular sciences · 2024Article
- Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress.Cell death discovery · 2024Article
- Growth hormone releasing hormone signaling promotes Th17 cell differentiation and autoimmune inflammation.Nature communications · 2023Article
- Growth hormone-releasing hormone antagonists protect against hydrochloric acid-induced endothelial injury in vitro.Environmental toxicology and pharmacology · 2023Article
- Growth Hormone-Releasing Hormone in Endothelial Inflammation.Endocrinology · 2022Review
- Growth hormone-releasing hormone receptor signaling in experimental ocular inflammation and neuroprotection.Neural regeneration research · 2022Review
- Neoantigen-based cancer vaccination using chimeric RNA-loaded dendritic cell-derived extracellular vesicles.Journal of extracellular vesicles · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The extrahypothalamic growth hormone-releasing hormone (GHRH) and its cognate receptors (GHRH-Rs) and splice variants are expressed in a variety of cancers. It has been shown that the pituitary type of GHRH-R (pGHRH-R) mediates the inhibition of tumor growth induced by GHRH-R antagonists. However, GHRH-R antagonists can also suppress some cancers that do not express pGHRH-R, yet the underlying mechanisms have not been determined. Here, using human esophageal squamous cell carcinoma (ESCC) as a model, we were able to reveal that SV1, a known splice variant of GHRH-R, is responsible for the inhibition induced by GHRH-R antagonist MIA-602. We demonstrated that GHRH-R splice variant 1 (SV1) is a hypoxia-driven promoter of tumor progression. Hypoxia-elevated SV1 activates a key glycolytic enzyme, muscle-type phosphofructokinase (PFKM), through the nuclear factor kappa B (NF-κB) pathway, which enhances glycolytic metabolism and promotes progression of ESCC. The malignant actions induced by the SV1-NF-κB-PFKM pathway could be reversed by MIA-602. Altogether, our studies demonstrate a mechanism by which GHRH-R antagonists target SV1. Our findings suggest that SV1 is a hypoxia-induced oncogenic promoter which can be an alternative target of GHRH-R antagonists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.