G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?
Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates...
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| Format: | Article |
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MDPI AG
2015-08-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/7/8/2959 |
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| author | Takeharu Kanazawa Kiyoshi Misawa Yuki Misawa Takayuki Uehara Hirofumi Fukushima Gen Kusaka Mikiko Maruta Thomas E. Carey |
| author_facet | Takeharu Kanazawa Kiyoshi Misawa Yuki Misawa Takayuki Uehara Hirofumi Fukushima Gen Kusaka Mikiko Maruta Thomas E. Carey |
| author_sort | Takeharu Kanazawa |
| collection | DOAJ |
| description | Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor. In this review, we discuss the roles that galanin receptor type 1 (GALR1) and type 2 (GALR2), tachykinin receptor type 1 (TACR1), and somatostatin receptor type 1 (SST1) play in HNSCC. GALR1 inhibits proliferation of HNSCC cells though ERK1/2-mediated effects on cell cycle control proteins such as p27, p57, and cyclin D1, whereas GALR2 inhibits cell proliferation and induces apoptosis in HNSCC cells. Hypermethylation of GALR1, GALR2, TACR1, and SST1 is associated with significantly reduced disease-free survival and a higher recurrence rate. Although their overall activities varies, each of these GPCRs has value as both a prognostic factor and a therapeutic target. These data indicate that further study of GPCRs is a promising strategy that will enrich pharmacogenomics and prognostic research in HNSCC. |
| first_indexed | 2024-04-11T13:16:30Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T13:16:30Z |
| publishDate | 2015-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-ed5e7a5ca5ca4f13b44d0fa782f19cc32022-12-22T04:22:23ZengMDPI AGToxins2072-66512015-08-01782959298410.3390/toxins7082959toxins7082959G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?Takeharu Kanazawa0Kiyoshi Misawa1Yuki Misawa2Takayuki Uehara3Hirofumi Fukushima4Gen Kusaka5Mikiko Maruta6Thomas E. Carey7Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University, Shimotsuke 329-0498, JapanLaboratory of Head and Neck Center Biology, Department of Otolaryngology, Head and Neck Surgery, the University of Michigan, Ann Arbor, MI 48109, USALaboratory of Head and Neck Center Biology, Department of Otolaryngology, Head and Neck Surgery, the University of Michigan, Ann Arbor, MI 48109, USADepartment of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, JapanDepartment of Head and Neck, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, JapanDepartment of Neurosurgery, Jichi Medical University Saitama Medical Center, Saitama 330-8503, JapanDepartment of Otolaryngology-Head and Neck Surgery, Jichi Medical University, Shimotsuke 329-0498, JapanLaboratory of Head and Neck Center Biology, Department of Otolaryngology, Head and Neck Surgery, the University of Michigan, Ann Arbor, MI 48109, USATherapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor. In this review, we discuss the roles that galanin receptor type 1 (GALR1) and type 2 (GALR2), tachykinin receptor type 1 (TACR1), and somatostatin receptor type 1 (SST1) play in HNSCC. GALR1 inhibits proliferation of HNSCC cells though ERK1/2-mediated effects on cell cycle control proteins such as p27, p57, and cyclin D1, whereas GALR2 inhibits cell proliferation and induces apoptosis in HNSCC cells. Hypermethylation of GALR1, GALR2, TACR1, and SST1 is associated with significantly reduced disease-free survival and a higher recurrence rate. Although their overall activities varies, each of these GPCRs has value as both a prognostic factor and a therapeutic target. These data indicate that further study of GPCRs is a promising strategy that will enrich pharmacogenomics and prognostic research in HNSCC.http://www.mdpi.com/2072-6651/7/8/2959head and neck neoplasmbiomarkertreatmentmolecular targeted therapy |
| spellingShingle | Takeharu Kanazawa Kiyoshi Misawa Yuki Misawa Takayuki Uehara Hirofumi Fukushima Gen Kusaka Mikiko Maruta Thomas E. Carey G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer? Toxins head and neck neoplasm biomarker treatment molecular targeted therapy |
| title | G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer? |
| title_full | G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer? |
| title_fullStr | G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer? |
| title_full_unstemmed | G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer? |
| title_short | G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer? |
| title_sort | g protein coupled receptors next generation therapeutic targets in head and neck cancer |
| topic | head and neck neoplasm biomarker treatment molecular targeted therapy |
| url | http://www.mdpi.com/2072-6651/7/8/2959 |
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