Wang Yang, Zhang Ling, He Zhiyan, Deng Jiong, Zhang Zhiyuan, Liu Liu, Ye Weimin, Liu Shuli
Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Am J Transl Res. 2020 Feb 15;12(2):541-550. eCollection 2020.
Glycosylation plays an important role in the genesis of various cancers. The inhibition of glycosylation disturbs the protein folding machinery, causing the accumulation of unfolded proteins in the cell endoplasmic reticulum (ER) and inducing ER stress. Tunicamycin (TM) is an inhibitor of glycosylation that has shown marked antitumor activity. In this study, we investigated the effect of TM on the tumorigenesis of head and neck cancer cells. The effects of TM on cell proliferation, colony formation and tumorsphere formation in and tumorigenicity in were investigated in head and neck cancer cells. ER stress was determined by the evaluation of PERK, PDI, IRE1-α, BIP, Ero1-Lα and calnexin expression using western blotting and immunofluorescence. We found that TM inhibited colony formation and tumorsphere formation of head and neck cancer cells in and suppressed tumor growth in . After incubation with TM, the expression of the cancer stem cell markers CD44 and Bmi-1 was reduced, and the expression of the ER stress markers BIP, Ero1-Lα and calnexin was elevated. Moreover, the EGFR signaling pathway was inhibited, and nonglycosylated EGFR degradation was accelerated with TM treatment. Our results suggest that inhibition of glycosylation by TM may be a novel treatment strategy for use with HNSCC patients.
糖基化在多种癌症的发生过程中起着重要作用。糖基化的抑制会干扰蛋白质折叠机制，导致未折叠蛋白在细胞内质网（ER）中积累，并诱导内质网应激。衣霉素（TM）是一种糖基化抑制剂，已显示出显著的抗肿瘤活性。在本研究中，我们研究了TM对头颈部癌细胞肿瘤发生的影响。在头颈部癌细胞中研究了TM对细胞增殖、集落形成和肿瘤球形成以及在体内的致瘤性的影响。通过蛋白质印迹法和免疫荧光法评估PERK、PDI、IRE1-α、BIP、Ero1-Lα和钙连接蛋白的表达来确定内质网应激。我们发现，TM抑制了头颈部癌细胞在体外的集落形成和肿瘤球形成，并在体内抑制了肿瘤生长。用TM处理后，癌症干细胞标志物CD44和Bmi-1的表达降低，内质网应激标志物BIP、Ero1-Lα和钙连接蛋白的表达升高。此外，EGFR信号通路受到抑制，TM处理加速了非糖基化EGFR的降解。我们的结果表明，TM抑制糖基化可能是一种用于头颈部鳞状细胞癌患者的新型治疗策略。
