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.