Abstract
BackgroundIncreased expression of integrin β1 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 β1 on the invasion and radioresistance of laryngeal cancer cells.MethodsThe expression of integrin β1 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.ResultsHigh expression of integrin β1 was significantly associated with lymph node metastasis, TNM stage and poor clinical outcomes (all p < 0.05). Knockdown of integrin β1 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 β1 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 β1 and CD147 relied on intact lipid rafts. Disruption of lipid rafts by methyl beta cyclodextrin in laryngeal cancer cells was able to reverse integrin β1-mediated malignant phenotypes.ConclusionsIntegrin β1 has potential as a therapeutic target in prevention and treatment of laryngeal cancer.
Highlights
Increased expression of integrin β1 has been reported to correlate with progression and therapy resistance in many types of cancers
High expression of integrin β1 in laryngeal cancer patients is associated with TNM stage, lymph node, and poor survival Immunohistochemistry was carried out to investigate the expression of integrin β1 in 60 laryngeal cancer tissues and 25 noncancerous laryngeal tissues
High expression of integrin β1 was positively correlated with TNM stage (p = 0.019) and lymph node metastasis (p = 0.005)
Summary
Increased expression of integrin β1 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 β1 on the invasion and radioresistance of laryngeal cancer cells. The most common treatment options for laryngeal cancer are radiation therapy, surgery and chemotherapy. Integrins activate various signaling pathways, which contribute to the regulation of cell proliferation, migration, invasion, and therapy resistance [6, 7]. Integrin β1 has been linked to therapeutic resistance including conventional radiotherapy and chemotherapy in various tumor entities [8,9,10,11]. The underlying mechanisms of how the increased expression of integrin β1 confers invasion and radioresistance of laryngeal cancer remain unclear
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