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

Sep 24, 2026

Aspirin suppresses progression and metastasis in multiple cancers, yet its role in non-small cell lung cancer (NSCLC) required clarification. The study investigated how aspirin affects NSCLC proliferation and metastasis through GPIHBP1-dependent regulation of CD36 localization. Blood and tissue samples from aspirin-treated and untreated NSCLC patients were profiled using RNA sequencing, while protein and gene expression were assessed by IHC, Western blotting, and qRT-PCR. Functional assays and xenograft experiments demonstrated that GPIHBP1 counteracts tumor growth and spread by modulating CD36 localization.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

Background and rationale

Methods

Results

Conclusions

Key findings and novelty

Aspirin impedes non-small cell lung cancer development via fine-tuning the CD36 localization regulated by GPIHBP1 Wei Liu1\#, Dujuan Qiao2\#, Jia Chen3, Ya Gao1, Katsuhiro Okuda4, Yoshihisa Shimada5, Linong Yao1 1Department of Critical Care Medicine, Tangdu Hospital of Air Force Military Medical University, Xi’an, China; 2Department of Anesthesiology & Perioperative Medicine (D), Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, China; 3The College of Life Sciences, Northwest University, Xi’an, China; 4Department of Thoracic and Pediatric Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 5Department of Thoracic Surgery, Tokyo Medical University, Tokyo, Japan Contributions: (I) Conception and design: L Yao; (II) Administrative support: L Yao; (III) Provision of study materials or patients: W Liu; (IV) Collection and assembly of data: D Qiao, W Liu; (V) Data analysis and interpretation: J Chen, Y Gao, K Okuda, Y Shimada; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. \#These authors contributed equally to this work. Correspondence to: Linong Yao, MD, PhD. Department of Critical Care Medicine, Tangdu Hospital of Air Force Military Medical University, No. 569 Xinsi Road, Baqiao District, Xi’an 710034, [China. Email: yaolin@fmmu.edu.cn](China. Email: yaolin@fmmu.edu.cn). Background: 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 . Methods: 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. Results: GPIHBP1 was downregulated and was increased by treatment with aspirin in lung cancer tissues. Furthermore, GPIHBP1 overexpression inhibited the migration, cell proliferation, and epithelialmesenchymal 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. Conclusions: 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. Keywords: Aspirin; glycosylphosphatidylinositol HDL-binding protein 1 (GPIHBP1); non-small cell lung cancer (NSCLC); proliferation; metastasis Submitted Dec 03, 2024. Accepted for publication Feb 19, 2025. Published online Feb 27, 2025. doi: 10.21037/tlcr-2024-1174 View this article at: [https://dx.doi.org/10.21037/tlcr-2024-1174](https://dx.doi.org/10.21037/tlcr-2024-1174) © AME Publishing Company. Transl Lung Cancer Res 2025;14(2):491-512 | [https://dx.doi.org/10.21037/tlcr-2024-1174](https://dx.doi.or

FAQs

What question does the study address about aspirin and NSCLC?

The study clarifies how aspirin inhibits NSCLC cell proliferation and metastasis, focusing on whether the effect depends on GPIHBP1-mediated regulation of CD36 localization.

How was GPIHBP1 expression evaluated in patients and tissues?

GPIHBP1 expression was determined using immunohistochemistry (IHC), Western blotting, and quantitative real-time PCR (qRT-PCR).

What mechanism links GPIHBP1 to tumor progression?

GPIHBP1 directly interacts with CD36; when GPIHBP1 is knocked down, CD36 localization is disrupted, promoting NSCLC progression and metastasis.

Sep 24, 2026

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