J Cancer 2017; 8(3):345-353. doi:10.7150/jca.16607

Research Paper

Twist1 Enhances Hypoxia Induced Radioresistance in Cervical Cancer Cells by Promoting Nuclear EGFR Localization

Hua Xiong1*, Xin Nie1*, Yanmei Zou1, Chen Gong1, Yang Li1, Hua Wu1, Hong Qiu1, Lin Yang1, Liang Zhuang1, Peng Zhang1, Jing Zhang1, Yihua Wang2, Huihua Xiong1✉

1. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
2. Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
*These authors contribute to this paper equally.

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Xiong H, Nie X, Zou Y, Gong C, Li Y, Wu H, Qiu H, Yang L, Zhuang L, Zhang P, Zhang J, Wang Y, Xiong H. Twist1 Enhances Hypoxia Induced Radioresistance in Cervical Cancer Cells by Promoting Nuclear EGFR Localization. J Cancer 2017; 8(3):345-353. doi:10.7150/jca.16607. Available from http://www.jcancer.org/v08p0345.htm

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Twist1 is a crucial transcription factor that regulates epithelial mesenchymal transition and involves in metastasis. Recent evidence suggests that Twist1 plays important role in hypoxia-induced radioresistance, but the underlying mechanism remains elusive. Here we investigated the change of Twist1 expression in human cervical squamous cancer cell line SiHa after hypoxia treatment. We also explored the role of Twist1 in radioresistance by manipulating the expression level of Twist1. We observed that hypoxia treatment elevated the expression of Twist1 in SiHa cells. Knockdown of Twist1 with siRNA increased the radiosensitivity of SiHa cells under hypoxia condition, accompanied by reduced levels of nuclear Epidermal Growth Factor Receptor (EGFR) and DNA-dependent protein kinase (DNA-PK). Conversely, overexpression of Twist1 led to increased radioresistance of SiHa cells, which in turn increased nuclear EGFR localization and expression levels of nuclear DNA-PK. Moreover, concomitant high expression of hypoxia-inducible factor-1α (HIF-1α) and Twist1 in primary tumors of cervical cancer patients correlated with the worse prognosis after irradiation treatment. Taken together, these data provide new insights into molecular mechanism underlying hypoxia-induced radioresistance in cervical cancer cells, and suggest that Twist1 is a promising molecular target to improve the efficacy of cancer radiotherapy.

Keywords: Twist1, Hypoxia, EGFR, radioresistance.