TRIM32-mediated ABI2 downregulation promotes anoikis resistance and metastasis by regulating EMT in lung adenocarcinoma.

Metastasis largely drives the high mortality of lung adenocarcinoma (LUAD), with anoikis resistance acting as a critical mediator in this process. This study aims to reveal the role and mechanism of ABI2 in anoikis resistance and LUAD metastasis. ABI2 expression levels and clinical value were analyzed using multiple databases. Functional studies were conducted in LUAD cells under attached or detached culture. The level of apoptosis was assessed by flow cytometry and Calcein-AM/EthD-1 staining. The metastasis ability was detected by transwell assay and lung metastasis model by tail vein injection. The ubiquitination effect of TRIM32 on ABI2 was analyzed by coimmunoprecipitation. This study revealed that ABI2 was significantly downregulated in LUAD tissues and anoikis-resistant LUAD cells. Functionally, ABI2 overexpression suppressed the anoikis resistance and LUAD metastasis, while ABI2 knockdown exerted the opposite effects. Mechanistically, ABI2 inhibited anoikis resistance by regulating epithelial-mesenchymal transition (EMT), thereby inhibiting tumor metastasis. EMT activation could rescue the effects of ABI2 on anoikis and metastasis. In addition, anoikis resistance modulated ABI2 ubiquitination by altering TRIM32 localization. Clinically, patients with low ABI2 and high TRIM32 experienced the worst prognosis in TCGA-LUAD. And a negative correlation between ABI2 and TRIM32 was further observed in both the public cohorts and the real-world cohort. In conclusion, ABI2 exerts tumor-suppressive effects in LUAD by inhibiting anoikis resistance and metastasis. The TRIM32‑ABI2‑EMT axis shows encouraging preclinical prospects, yet sufficient follow-up studies are indispensable to support its clinical therapeutic potential.