Karyopherin-β1 Regulates Radioresistance and Radiation-Increased Programmed Death-Ligand 1 Expression in Human Head and Neck Squamous Cell Carcinoma Cell Lines.

Masaharu Hazawa,Reina Shimizume,Mariko Sato,Yoshiaki Sato,Keisuke Nitta,Yuta Nakagawa,Hironori Yoshino,Richard W Wong,Ikuo Kashiwakura

doi:10.3390/cancers12040908

Masaharu Hazawa, Reina Shimizume + Show 7 more

Open Access

https://doi.org/10.3390/cancers12040908

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Journal: Cancers	Publication Date: Apr 8, 2020
Citations: 9	License type: CC BY 4.0

Affiliation: Hirosaki University, Kanazawa University

Abstract

Nuclear transport receptors, such as karyopherin-β1 (KPNB1), play important roles in the nuclear-cytoplasmic transport of macromolecules. Recent evidence indicates the involvement of nuclear transport receptors in the progression of cancer, making these receptors promising targets for the treatment of cancer. Here, we investigated the anticancer effects of KPNB1 blockage or in combination with ionizing radiation on human head and neck squamous cell carcinoma (HNSCC). HNSCC cell line SAS and Ca9-22 cells were used in this study. Importazole, an inhibitor of KPNB1, or knockdown of KPNB1 by siRNA transfection were applied for the blockage of KPNB1 functions. The roles of KPNB1 on apoptosis induction and cell surface expression levels of programmed death-ligand 1 (PD-L1) in irradiated HNSCC cells were investigated. The major findings of this study are that (i) blockage of KPNB1 specifically enhanced the radiation-induced apoptosis and radiosensitivity of HNSCC cells; (ii) importazole elevated p53-upregulated modulator of apoptosis (PUMA) expression via blocking the nuclear import of SCC-specific oncogene ΔNp63 in HNSCC cells; and (iii) blockage of KPNB1 attenuated the upregulation of cell surface PD-L1 expression on irradiated HNSCC cells. Taken together, these results suggest that co-treatment with KPNB1 blockage and ionizing radiation is a promising strategy for the treatment of HNSCC.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is a lethal malignancy arising from the regions of the head and neck, such as the pharynx and oral cavity
The Kaplan–Meier analysis on the TCGA cohorts showed that head and neck squamous cell carcinoma (HNSCC) patients with high expressions of KPNB1 resulted in a poor outcome (Figure 1B)
These findings imply that KPNB1 is related to the malignancy of HNSCC; we examined whether KPNB1 is functionally

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is a lethal malignancy arising from the regions of the head and neck, such as the pharynx and oral cavity. The cumulative incidence of HNSCC was approximately 890,000 new cases in 2018, and it ranks as the seventh most common cancer types worldwide [1,2]. In spite of combined treatment involving surgery, radiation therapy, and chemotherapy, the five-year survival rate of HNSCC patients is low, and the prognosis is still poor [3]. Cancers 2020, 12, 908 evidence indicates that ionizing radiation increases cell surface programmed death-ligand 1 (PD-L1). In order to overcome these responses, the development of an effective strategy is desired for the treatment of HNSCC

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