Gao Wei, Xu Shaowei, Zhang Minjuan, Liu Shuai, Siu Sharie Pui-Kei, Peng Hanwei, Ng Judy Chun-Wai, Tsao George Sai-Wah, Chan Anthony Wing-Hung, Chow Velda Ling-Yu, Chan Jimmy Yu-Wai, Wong Thian-Sze
Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong 21 Sassoon Road, Pokfulam, Hong Kong, China.
Department of Head and Neck Surgery, Cancer Hospital of Shantou University Medical College 7 Raoping Road, Shantou 515031, Guangdong Province, China.
Am J Cancer Res. 2020 Jun 1;10(6):1710-1727. eCollection 2020.
Oral tongue squamous cell carcinoma (OTSCC) has a distinctive cell sub-population known as tumor-initiating cells (TICs). CD271 is a functional TIC receptor in head and neck cancers. The molecular mechanisms governing CD271 up-regulation remains unclear. Oxidative stress is a contributing factor in TIC development. Here, we explored the potential role of NADPH oxidase 5 (NOX5) and its regulatory mechanism on the development of CD271-expressing OTSCC. Our results showed that the splice variant NOX5α is the most prevalent form expressed in head and neck cancers. NOX5α enhanced OTSCC proliferation, migration, and invasion. Overexpression of NOX5α increased the size of OTSCC xenograft significantly in vivo. The tumor-promoting functions of NOX5α were mediated through the reactive oxygen species (ROS)-generating property. NOX5α activated ERK singling and increased CD271 expression at the transcription level. Also, NOX5α reduces the sensitivity of OTSCC to cisplatin and natural killer cells. The findings indicate that NOX5α plays an important part in the development of TIC in OTSCC.
口腔舌鳞状细胞癌（OTSCC）具有一种独特的细胞亚群，称为肿瘤起始细胞（TICs）。CD271是头颈癌中的一种功能性TIC受体。CD271上调的分子机制尚不清楚。氧化应激是TIC发展的一个促成因素。在此，我们探讨了NADPH氧化酶5（NOX5）的潜在作用及其对表达CD271的OTSCC发展的调控机制。我们的结果表明，剪接变体NOX5α是头颈癌中表达最普遍的形式。NOX5α增强了OTSCC的增殖、迁移和侵袭。在体内，NOX5α的过表达显著增加了OTSCC异种移植瘤的大小。NOX5α的促肿瘤功能是通过产生活性氧（ROS）的特性介导的。NOX5α激活ERK信号并在转录水平上增加CD271的表达。此外，NOX5α降低了OTSCC对顺铂和自然杀伤细胞的敏感性。这些发现表明，NOX5α在OTSCC中TIC的发展中起重要作用。
