ArticleMolecular cancer therapeutics2014
The G protein-coupled receptor GALR2 promotes angiogenesis in head and neck cancer.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- A Rare Case of Cutaneous Metastasis From Oral Squamous Cell Carcinoma (OSCC) and the Possible Role of GALR2 as a Biomarker: A Case Report.Clinical case reports · 2026Article
- Functional interplay between TTP/ZFP36 and HuR/ELAVL1 in cancer: a post-transcriptional regulatory network.Frontiers in oncology · 2026Review
- Identification and validation of a hypoxia- and immune-related prognostic signature for pancreatic cancer.Biochemistry and biophysics reports · 2025Article
- Cancer neuroscience in head and neck: interactions, modulation, and therapeutic strategies.Molecular cancer · 2025Review
- Understanding the role of nerves in head and neck cancers - a review.Oncology reviews · 2024Review
- Nuclear Epidermal Growth Factor Receptor Overexpression as a Survival Predictor in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2023Article
- Important Cells and Factors from Tumor Microenvironment Participated in Perineural Invasion.Cancers · 2023Review
- MAPK Signaling Pathway in Oral Squamous Cell Carcinoma: Biological Function and Targeted Therapy.Cancers · 2022Review
- Comprehensive Characterization of Immune Landscape Based on Tumor Microenvironment for Oral Squamous Cell Carcinoma Prognosis.Vaccines · 2022Article
- The Galaninergic System: A Target for Cancer Treatment.Cancers · 2022Review
- Galanin mediates tumor-induced immunosuppression in head and neck squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Galanin Receptors (GalR1, GalR2, and GalR3) Expression in Colorectal Cancer Tissue and Correlations to the Overall Survival and Poor Prognosis of CRC Patients.International journal of molecular sciences · 2022Article
- Tristetraprolin, a Potential Safeguard Against Carcinoma: Role in the Tumor Microenvironment.Frontiers in oncology · 2021Review
- Cluster Analysis of Early Postnatal Biochemical Markers May Predict Development of Retinopathy of Prematurity.Translational vision science & technology · 2020Article
- The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects.Cancers · 2020Review
- The p38/MKP-1 signaling axis in oral cancer: Impact of tumor-associated macrophages.Oral oncology · 2020Review
- The Chick Chorioallantoic Membrane In Vivo Model to Assess Perineural Invasion in Head and Neck Cancer.Journal of visualized experiments : JoVE · 2019Article
- Galanin expression is down-regulated in patients with gastric cancer.The Journal of international medical research · 2019Article
- Roles of Tristetraprolin in Tumorigenesis.International journal of molecular sciences · 2018Review
- CD90 determined two subpopulations of glioma-associated mesenchymal stem cells with different roles in tumour progression.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor patient survival. Galanin receptor 2 (GALR2) is a G protein-coupled receptor that induces aggressive tumor growth in SCCHN. The objective of this study was to investigate the mechanism by which GALR2 promotes angiogenesis, a critical oncogenic phenotype required for tumor growth. The impact of GALR2 expression on secretion of proangiogenic cytokines in multiple SCCHN cell lines was investigated by ELISA and in vitro angiogenesis assays. Chemical inhibitor and genetic knockdown strategies were used to understand the key regulators. The in vivo impact of GALR2 on angiogenesis was investigated in mouse xenograft, chick chorioallantoic membrane, and the clinically relevant mouse orthotopic floor-of-mouth models. GALR2 induced angiogenesis via p38-MAPK-mediated secretion of proangiogenic cytokines, VEGF, and interleukin-6 (IL-6). Moreover, GALR2 activated small-GTP-protein, RAP1B, thereby inducing p38-mediated inactivation of tristetraprolin (TTP), which functions to destabilize cytokine transcripts. This resulted in enhanced secretion of proangiogenic cytokines and angiogenesis in vitro and in vivo. In SCCHN cells overexpressing GALR2, inactivation of TTP increased secretion of IL-6 and VEGF, whereas inhibition of p38 activated TTP and decreased cytokine secretion. Here, we report that GALR2 stimulates tumor angiogenesis in SCCHN via p38-mediated inhibition of TTP with resultant enhanced cytokine secretion. Given that p38 inhibitors are in clinical use for inflammatory disorders, GALR2/p38-mediated cytokine secretion may be an excellent target for new adjuvant therapy in SCCHN.
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Registered trials
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