title: Repression of GPRC5A is associated with activated STAT3, which contributes to tumor progression of head and neck squamous cell carcinoma.
abstract: BACKGROUND
  G protein-coupled receptor family C group 5 member A (GPRC5A), a retinoic acid-inducible gene, is a lung tumor suppressor. Previously, we showed that repression of GPRC5A expression was associated with pathologic differentiation grade of oral squamous cell carcinomas (OSCC) and overexpression of GPRC5A gene inhibited the malignant phenotype in OSCC cells, suggesting that GPRC5A also functions as a tumor suppressor in oral cancer. However, the molecular mechanisms underlying GPRC5A deficiency in head and neck squamous cell carcinoma (HNSCC) are still unclear.
  
  
  METHODS
  In this study, we used Western blot analysis and immunohistochemical (IHC) staining to investigate the expression of GPRC5A in both HNSCC cell lines and clinical samples. GPRC5A stable transfectants and their parental HNSCC cells were characterized for their biological activities in anchorage-independent growth.
  
  
  RESULTS
  IHC analysis showed that, GPRC5A expression was high in normal tissue, but gradually decreased in oral leukoplakia, a precancerous stage, and greatly suppressed in primary cancer. Repression of GPRC5A was correlated with activated STAT3, which associates with aggressive clinicopathological features in HNSCC patients. Moreover, overexpression of GPRC5A suppressed IL-6-induced-STAT3 activation and inhibited anchorage-independent growth in HNSCC cells.
  
  
  CONCLUSIONS
  Repressed GPRC5A associates with increased tumor grade and activated STAT3, which may be used as a prognostic marker for tumor progression of HNSCC.
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Ye
authors.affiliation: Key laboratory of cell differentiation and apoptosis of Chinese Minister of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key laboratory of cell differentiation and apoptosis of Chinese Minister of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Guo
authors.affiliation: Key laboratory of cell differentiation and apoptosis of Chinese Minister of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Song
authors.affiliation: Key laboratory of cell differentiation and apoptosis of Chinese Minister of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yueling
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Key laboratory of cell differentiation and apoptosis of Chinese Minister of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hanguang
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key laboratory of cell differentiation and apoptosis of Chinese Minister of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Deng
keywords: GPRC5A; HNSCC; Leukoplakia; Prognostic marker; STAT3