| Popis: |
Background: The role of tetraspanins in cancer development has been widely reported. However, the expression and roles of tetraspanin 3 (TSPAN3) in solid tumors, including non-small cell lung cancer (NSCLC), have not yet been extensively investigated. In this study, we explored the role of TSPAN3 in NSCLC and its potential role in the trafficking of integrin β1, which is highly expressed in this type of cancer.Methods: The expression of TSPAN3 in NSCLC tissue and NSCLC cell lines was evaluated, and the correlation between TSPAN3 expression and disease progression was assessed. Furthermore, loss- and gain-of-expression studies were conducted to determine the biological function of TSPAN3 both in vivo and vitro. The regulatory role of TSPAN3 in β1 integrin expression and intracellular recycling was studied through western blot, RT-PCR, and immunofluorescence analyses.Results: TSPAN3 was found to be highly expressed in lung cancer cells and tissues. Moreover, high levels of TSPAN3 positively correlated with poor differentiation, lymph node involvement, advanced pathological tumor-node-metastasis stage, and poor prognosis in NSCLC patients. TSPAN3 showed the potential to promote the proliferation of NSCLC cells in vitro and in vivo. Specifically, TSPAN3 was found to interact with β1 integrin and Rab11a, thereby facilitating the sorting of β1 integrin into Rab11a endosomes and promoting β1 integrin recycling and upregulation. Conclusions: These findings reveal a novel role for TSPAN3 in the regulation of intracellular recycling of β1 integrin. Hence, TSPAN3 may represent a potentially valuable therapeutic target for NSCLC. |
