Effect of ABHD4 on biological behavior of small cell lung cancer and its mechanism of action

Background: Small cell lung cancer (SCLC) is a highly aggressive malignancy with limited therapeutic options. ABHD4, a member of the lipid-metabolizing enzyme family, has been implicated in various cancers, but its precise role and molecular mechanisms in SCLC remain poorly understood. The aim of this study was to investigate the functional impact of ABHD4 on SCLC progression and to explore its potential links with lipid metabolism and the PI3K/AKT/mTOR signaling pathway. Methods: The study analyzed ABHD4 expression in clinical SCLC specimens and cell lines. Functional characterization was performed using ABHD4 knockdown in xenograft models and cancer cells to assess effects on tumor growth, proliferation, migration, invasion, and apoptosis. Metabolomic profiling was employed to examine lipid metabolism changes. Mechanistic studies focused on the PI3K/AKT/mTOR pathway, and curcumin treatment was used to interrogate ABHD4-associated phenotypes in H69 cells. Results: ABHD4 was consistently upregulated in SCLC samples compared to normal controls. Its knockdown significantly impaired tumor growth in vivo and reduced cancer cell proliferation, migration, and invasion while promoting apoptosis. Metabolomic analysis confirmed a connection between ABHD4 expression and altered lipid metabolism. Mechanistically, ABHD4 was identified as a key factor associated with the PI3K/AKT/mTOR pathway. Furthermore, curcumin treatment effectively attenuated the oncogenic phenotypes linked to ABHD4 overexpression. Conclusions: This study demonstrates that ABHD4 contributes to SCLC progression, associates with modulations in lipid metabolism, and is linked to the PI3K/AKT/mTOR signaling pathway. The findings suggest ABHD4 as a potential therapeutic target, with curcumin showing promise in mitigating its oncogenic effects.