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Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

 Woo Jin Bae  ;  Bon Seok Koo  ;  Sang Hyuk Lee  ;  Jin Man Kim  ;  Young Soo Rho  ;  Jae Yol Lim  ;  Jung Hwa Moon  ;  Jae Hoon Cho  ;  Young Chang Lim 
 BRITISH JOURNAL OF CANCER, Vol.117(12) : 1810-1818, 2017 
Journal Title
Issue Date
Animals ; Antineoplastic Agents/pharmacology ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Cell Self Renewal/genetics ; Cell Survival/drug effects ; Cisplatin/pharmacology ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression ; Gene Silencing ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/metabolism* ; Humans ; Hyaluronan Receptors/metabolism ; Inhibitor of Differentiation Protein 2/genetics* ; Inhibitor of Differentiation Protein 2/metabolism* ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation/pathology ; Neoplastic Stem Cells/metabolism* ; Phenotype ; Spheroids, Cellular ; Survival Rate
BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are highly lethal epithelial tumours containing self-renewal cancer stem cells (CSCs). CSCs in HNSCCs are strongly associated with tumour initiation, invasion, and chemoradiation resistance. However, the important factors regulating stemness in HNSCCs remain unclear. Here, we investigated the molecular roles and clinical significance of inhibitor of DNA binding 2 (Id2) protein to determine if it constitutes a novel therapeutic target for ablating HNSCC cells with stemness. METHODS: We performed in vitro and in vivo studies of Id2 function and its effects on stemness using HNSCC cells. We also examined whether Id2 expression could be used as a prognostic indicator through immunohistochemical staining of 119 human HNSCC tumours. RESULTS: Expression of Id2 was higher in HNSCC cells with stemness compared with differentiated HNSCC cells. Overexpression of Id2 increased proliferation, self-renewal, and expression of the putative stemness marker CD44 in HNSCC cells in vitro and in vivo. In contrast, silencing of Id2 using short hairpin RNA attenuated the stemness phenotype of HNSCC cells by reducing self-renewal, CD44 expression, cisplatin chemoresistance, and xenograft tumourigenicity. Most importantly, increased expression of Id2 was closely associated with poorer post-treatment survival rates in HNSCC patients. CONCLUSIONS: Inhibitor of DNA binding2 represents a novel and promising therapeutic target for treating and improving the clinical outcomes for patients with HNSCC.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Lim, Jae Yol(임재열) ORCID logo https://orcid.org/0000-0002-9757-6414
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