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Br J Cancer. 2017 Dec 5;117(12):1810-1818. doi: 10.1038/bjc.2017.373. Epub 2017 Nov 2.

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

Author information

1
Department of Otorhinolaryngology - Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, No. 1, Hwayang-dong, Gwangin-gu, 120-1 Neungdong ro, Seoul 143-752, South Korea.
2
Department of Otolaryngology - Head and Neck Surgery, Cancer Research Institute, Research Institute for Medical Sciences and Pathology, Daejeon 301-721, South Korea.
3
Department of Otorhinolaryngology - Head and Neck Surgery, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul 110-746, South Korea.
4
Chungnam National University College of Medicine, Daejeon 301-721, South Korea.
5
Department of Otolaryngology - Head and Neck Surgery, Hallym University College of Medicine, Seoul 134-701, South Korea.
6
Department of Otorhinolaryngology, Yonsei University School of Medicine, Seoul 06273, South Korea.

Abstract

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.

PMID:
29096401
PMCID:
PMC5729481
DOI:
10.1038/bjc.2017.373
[Indexed for MEDLINE]
Free PMC Article

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