Enhanced chemosensitivity by targeting Nanog in head and neck squamous cell carcinomas.

Chuan-En Huang,Fang-Wei Hu,Cheng-Chia Yu,Ming-Yung Chou,Lo-Lin Tsai

doi:10.3390/ijms150914935

Abstract

Chemo-resistance is the major cause of high mortality in head and neck squamous cell carcinomas (HNSCC) in which HNSCC-derived cancer stem cells (CSCs) may be involved. Previously, we enriched a subpopulation of HNSCC-derived spheroid cells (SC) (HNSCC-SC) and identified Nanog as a CSCs marker. The aim of this study was to determine the role of Nanog in the chemosensitivity of HNSCC. The functional and clinicopathological studies of Nanog were investigated in HNSCC cells and specimens. Nanog expression was increased in HNSCC cell lines as compared to a normal oral epithelial cell line. Nanog upregulation in clinical tissues from HNSCC patients with recurrent and metastatic specimens relative to the mRNA levels in the samples from normal or primary tissues were examined. Targeting Nanog in HNSCC-SC significantly inhibited their tumorigenic and CSCs-like abilities and effectively increased the sensitivity of HNSCC-SC to chemotherapeutic drug cisplatin treatment. Targeting Nanog in HNSCC-SC showed a synergistic therapeutic effect with cisplatin. Our results suggest that targeting Nanog may have promising therapeutic potential for HNSCC.

Highlights

Head and neck squamous cell carcinomas (HNSCC) are a worldwide public health problem, and the incidence of HNSCC is increasing worldwide [1]
Strong expression of Nanog is shown as an indicator of a poor prognosis for ovarian serous carcinoma, colorectal and breast cancer patients [21,22,23]
Our results suggest that small hairpin RNA (shRNA)-mediated knockdown of Nanog can effectively block cancer stem cells (CSCs)-like properties and increase the sensitivity of HNSCC-CSCs to cisplatin treatment and induced cell apoptosis

Summary

Introduction

Head and neck squamous cell carcinomas (HNSCC) are a worldwide public health problem, and the incidence of HNSCC is increasing worldwide [1]. To increase the patient survival rate, investigations elucidating the mechanisms of tumorigenicity in HNSCC are urgently needed. Some studies have suggested that the subsets of cancer stem cells (CSCs) are key contributors to chemo-radio-resistance and are responsible for tumor progression, as well as recurrence after conventional therapy [2,3,4]. Development of CSC-specific targeting therapeutics could improve efficacies and increase the HNSCC patient survival rate and, has become a prospective direction for cancer therapy. Nanog is a key transcription factor that is involved in the maintenance of pluripotency and self-renewal in undifferentiated embryonic stem (ES) cells [5]. A recent study revealed that a short sequence in the well-conserved homeobox domain of Nanog was sufficient to induce pluripotency in Nanog-deficient somatic cells, indicating a crucial role of the homeobox domain in mediating the reprogramming ability of

Objectives

Results

Conclusion