Desmoglein-2 promotes the proliferation and invasion of lung adenocarcinoma cells by inhibiting anoikis through the activation of the integrin beta-1/focal adhesion kinase signaling pathway.

Patients with advanced lung adenocarcinoma often develop metastasis and recurrence, leading to treatment failure. Anoikis resistance is a key step in tumor metastasis. Desmoglein-2 (DSG2) plays an important role in several cancers; however, its role in lung adenocarcinoma and its relationship to anoikis remain unclear. In this study, we aimed to investigate whether DSG2 regulates proliferation, invasion, and anoikis in lung adenocarcinoma cells and to explore the underlying mechanism. We analyzed DSG2 expression in lung cancer tissues and cells using online databases, examining the effects of DSG2 knockdown and overexpression on proliferation, invasion, and anoikis in lung adenocarcinoma cell models. Furthermore, we examined whether DSG2 functions through the integrin β1/focal adhesion kinase (FAK) signaling pathway and evaluated the effects of the integrin β1 agonist Pyrintegrin. DSG2 was highly expressed in lung adenocarcinoma tissues and cells and was associated with poor prognosis. DSG2 knockdown inhibited proliferation and invasion and promoted anoikis, whereas DSG2 overexpression increased invasion and proliferation and suppressed anoikis. Mechanistic analysis revealed that DSG2 activated the integrin β1/FAK signaling pathway. Pyrintegrin reversed the inhibitory effects of DSG2 knockdown on lung adenocarcinoma cells. DSG2 inhibits anoikis in lung adenocarcinoma cells by activating the integrin β1/FAK signaling pathway, thereby promoting cell proliferation and invasion.