Tetraspanin 3 promotes NSCLC cell proliferation via regulation of β1 integrin intracellular recycling.

Background: The involvement of tetraspanins in cancer development has been widely implicated. In this study, the function and molecular mechanisms of tetraspanin 3 (TSPAN3) in non-small cell lung cancer (NSCLC) cells were explored.

Methods: Tissue samples from patients diagnosed with NSCLC were analyzed by immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) to indicate the involvement of TSPAN3 in cancer progression. In the meantime, we also performed exhaustive mechanistic studies using A549 and H460 cells in vitro through a variety of methods including western blotting, real-time PCR, immunofluorescent staining, coimmunoprecipitation, cell proliferation assay, and nocodazole (NZ) washout assay. Proper statistical analysis was implemented wherever necessary in this study.

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 patients with NSCLC. TSPAN3 showed potential to promote the proliferation of NSCLC cells in vitro and in vivo. Specifically, TSPAN3 was found to interact with β1 integrin via the LEL domain, thereby facilitating the sorting of β1 integrin into Rab11a endosomes and promoting β1 integrin recycling and upregulation.

Conclusions: Our findings reveal TSPAN3 may represent a potentially valuable therapeutic target for NSCLC.