Growth Regulated Oncogene-? Upregulates TNF-? and COX-2 and Activates NOD1/RIPK2 mediated-MAPK Pathway in Head and Neck Squamous Cell Carcinoma

doi:10.7150/jca.82300

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Title:	Growth Regulated Oncogene-? Upregulates TNF-? and COX-2 and Activates NOD1/RIPK2 mediated-MAPK Pathway in Head and Neck Squamous Cell Carcinoma
Authors:	Chan, Leong-Perng Tseng, Ya-Ping Wang, Hui-Ching Chien, Chen -Yu Wu, Che-Wei Wang, Ling-Feng Liang, Chia-Hua
Contributors:	Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Coll Med, Fac Med,Dept Otorhinolaryngol Head & Neck Surg Kaohsiung Med Univ, Kaohsiung Municipal Ta Tung Hosp, Dept Otorhinolaryngol Head & Neck Surg Natl Cheng Kung Univ, Inst Basic Med Sci Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Internal Med, Div Hematol & Oncol Kaohsiung Med Univ, Kaohsiung Municipal Siaogang Hosp, Dept Otolaryngol Head & Neck Surg Chia Nan Univ Pharm & Sci, Dept Cosmet Sci Chia Nan Univ Pharm & Sci, Inst Cosmet Sci
Keywords:	HNSCC Gro? NOD1 MAPK Metastasis
Date:	2023
Issue Date:	2024-12-25 11:05:28 (UTC+8)
Publisher:	IVYSPRING INT PUBL
Abstract:	Purpose: The long-term prognosis and survival rate of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are poor, although the identification of specific biomarkers that reveal its nature and aggressiveness has improved it. Growth-related oncogene alpha (Gro alpha) and NOD1 (nucleotide-binding oligomerization domain 1) can be used as prognosis markers to identify subgroups of HNSCC patients with low survival rates and as potential therapeutic targets for HNSCC patients. However, the mechanism associated with the Gro alpha-mediated NOD pathway in HNSCC progression remains unclear. Method: Overall survival analysis and multiple-gene comparison were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA). qRT-PCR and RT-PCR were used to analyze mRNA expression. Microarray, immunofluorescence staining or western blot analyses were carried out to detect protein expression. Results: Gro alpha was significantly higher in the grade 4 HNSCC tumor tissues compared with that in grade 1-3 and healthy subjects. High expression of Gro alpha, NOD1 and RIPK2 (receptor-interacting serine-threonine kinase 2) is correlated with survival rate in HNSCC patients. Treatment of SCC25 and OECM-1 cells with Gro alpha increased the expression of NOD1 and RIPK2 in a concentration-dependent manner. The findings herein reveal the association of Gro alpha, NOD1 and RIPK2 biomarkers with HNSCC carcinogenesis. Moreover, Gro alpha is the major stimulus of inflammatory mediation and promotes TNF-alpha (tumor necrosis factor-alpha) and COX-2 (cyclooxygenase-2) expression in HNSCC. Gro alpha induces TNF-alpha and COX-2 expression through regulation involving ERK (extracellular signal-regulated kinase)-, JNK (C-Jun N-terminal kinase)-and p38 MAPK (mitogen-activated protein kinase)-dependent signaling pathways. Conclusions: Our findings herein constitute the first evidence that Gro alpha is important in HNSCC progression and metastasis via the NOD1-mediated MAPK pathway, suggesting a role for Gro alpha and NOD1 in mediating metastasis and its potential as a therapeutic target.
Relation:	Journal of Cancer, v.14, n.6, pp.989-1000
Appears in Collections:	[Offices] 456

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