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Solute Carrier Family 2 Member 4 Regulates TRIM24‐DDX58 Axis to Promote Head and Neck Cancer Metastasis
Author(s) -
Chang YuChan,
Hsiao Michael
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.808.5
Subject(s) - head and neck squamous cell carcinoma , cancer research , gene knockdown , carcinogenesis , biology , cancer , head and neck cancer , cell culture , genetics
Metabolic reprogramming and aerobic glycolysis has been observed in head and neck squamous cell carcinoma (HNSCC) involved tumor metastasis and tumorigenesis. Solute carrier family (SLC) members present as a major hub in glycolysis pathway by accelerated metabolic rate. However, solute carrier family 2 member 4's (SLC2A4) role in HNSCC has not been fully investigated. In this study, we identified the SLC2A4 had most significant value and ranking associated with HNSCC survival rate and metastasis status than other family members via in silico database analysis. Furthermore, immunohistochemistry analysis also showed consistency result that SLC2A4 is positive correlated with N status. In addition, our clinicopathologic analysis showed that an increased SLC2A4 expression in HNSCC patients was associated with a significant poor overall survival (OS, p =0.035) and recurrence‐free survival (RFS, P = 0.001). Two‐way complementary models including overexpression or knockdown of SLC2A4 were preformed and identified SLC2A4 overexpression promoted HNSCC migration and invasion in vitro and in vivo . SLC2A4‐overexpressed FaDu cell line was used to perform gene expression microarray to determine the underneath molecular mechanisms. Ingenuity Pathway Analysis (IPA) software was utilized and identified tripartite motif‐containing 24 (TRIM24) transcription factor was a leading downstream regulator of SLC2A4. DDX58 was further confirmed to be the main downstream target of TRIM24 whose down‐regulation was found essential for the migratory phenotype induced by SLC2A4‐TRIM24 activation in our model. Finally, combined SLC2A4 with DDX58 could be used as a strong independent prognosis marker that is significantly correlated with poor survival rate in HNSCC patients. This novel signaling axis may be used for therapeutics development of HNSCC in the near future.