Aspirin impedes non-small cell lung cancer development via fine-tuning the CD36 localization regulated by GPIHBP1

Lung cancer, a commonly diagnosed malignancy, is the leading cause of cancer-related death worldwide. Aspirin suppresses the progression and metastasis of various cancers. However, the effect of aspirin on non-small cell lung cancer (NSCLC) has not been fully understood. It has been established that glycosylphosphatidylinositol HDL-binding protein 1 (GPIHBP1) and CD36 play a vital role in lipid metabolism and transport. This study aimed to clarify the mechanism by which aspirin inhibits NSCLC cell proliferation and metastasis via GPIHBP1.

The blood and tissues of 10 patients with NSCLC treated with aspirin and 10 patients without aspirin were collected and analyzed via RNA sequencing. GPIHBP1 expression was determined by immunohistochemistry (IHC), Western blotting, and quantitative real time polymerase chain reaction (qRT-PCR). A series of functional experiments were performed to evaluate the effects of aspirin on NSCLC progression in a GPIHBP1-dependent manner. The potential mechanism of GPIHBP1 was explored via coimmunoprecipitation and immunofluorescence staining. The effect of GPIHBP1 on tumor growth and metastasis was verified by constructing subcutaneous xenograft tumor model in nude mice.

GPIHBP1 was downregulated and was increased by treatment with aspirin in lung cancer tissues. Furthermore, GPIHBP1 overexpression inhibited the migration, cell proliferation, and epithelial-mesenchymal transition process in NSCLC cells while promoting their apoptosis, while in cells with GPIHBP1 knockdown, the opposite was observed. Mechanistically, GPIHBP1 directly interacted with CD36 while GPIHBP1 knockdown disrupted CD36 localization, thus promoting tumor progression and metastasis in NSCLC cells. In addition, through in vivo xenograft experiments, we found that GPIHBP1 overexpression inhibited tumor growth and metastasis.

Our findings provide new insights into the mechanism by which aspirin suppresses lung cancer development in a GPIHBP1-dependent manner and may provide a promising target in NSCLC treatment.