Integrin β1 regulates the invasion and radioresistance of laryngeal cancer cells by targeting CD147

Background: Increased expression of integrin beta 1 has been reported to correlate with progression and therapy resistance in many types of cancers. The aim of this study was to investigate the effects of integrin beta 1 on the invasion and radioresistance of laryngeal cancer cells. Methods: The expression of integrin beta 1 in the tumor specimens of laryngeal cancer patients was assessed by immunohistochemical assays. The invasion ability of laryngeal cancer cells was detected by transwell and wound healing assays. The radiosensitivity of laryngeal cancer cells was evaluated by flow cytometry and colony formation assays. Results: High expression of integrin beta 1 was significantly associated with lymph node metastasis, TNM stage and poor clinical outcomes (all p<0.05). Knockdown of integrin beta 1 in laryngeal cancer cells inhibited invasion and increased radiosensitivity. Mechanistically, these effects were caused by suppression of the downstream focal adhesion kinase (FAK)/cortactin pathway. In addition, integrin beta 1 could interact with CD147 and the antibody blockade of CD147 led to the deactivation of FAK/cortactin signaling. Further studies revealed that the interaction between integrin beta 1 and CD147 relied on intact lipid rafts. Disruption of lipid rafts by methyl beta cyclodextrin in laryngeal cancer cells was able to reverse integrin beta 1-mediated malignant phenotypes. Conclusions: Integrin beta 1 has potential as a therapeutic target in prevention and treatment of laryngeal cancer.