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image of ARL6IP1 Inhibits Breast Cancer Tumor Progression by Targeting OLFM4 to Regulate Glycolysis

Abstract

Introduction

ARL6IP1 has been linked to cancer progression, but its precise role in BC, particularly in metabolism and its interaction with an OLFM4, remains unclear.

Aims

This study aimed to investigate the role of ADP-ribosylation factor-like 6 interacting protein 1 (ARL6IP1) in breast cancer (BC) cell behavior and metabolism and explore its interaction with an olfactomedin-4 (OLFM4) as a potential therapeutic target.

Objective

The objective of this study was to determine the effects of knockdown on BC cell proliferation, invasion, migration, apoptosis, oxidative stress, and glycolysis. Additionally, this study also explored the interaction between ARL6IP1 and OLFM4 and their combined role in BC progression and metabolism.

Methods

Key gene modules in the GSE73540 dataset were identified through weighted gene co-expression network analysis (WGCNA). Three BC-related datasets (GSE73540, GSE22820, and GSE36295) and The Cancer Genome Atlas (TCGA) were applied for additional examination of differentially expressed genes (DEGs). Intersection analysis selected as a hub gene for prognostic analysis. In experiments investigated how knockdown influences BC cell proliferation, invasion, migration, apoptosis, epithelial-mesenchymal transition (EMT), oxidative stress, and glycolysis. The connection between ARL6IP1 and an OLFM4 was confirmed using Co-immunoprecipitation (Co-IP), and their roles in BC tumor progression and glycolysis were evaluated.

Results

was elevated in BC datasets and linked with poor BC prognosis. Experiments demonstrated that knockdown of significantly reduced BC cell growth while promoting apoptosis and oxidative stress. Besides, knockdown reduced glycolysis, as manifested by decreased extracellular acidification rate (ECAR), glucose consumption, adenosine triphosphate (ATP) levels, and lactate production while increasing mitochondrial respiration (OCR). Co-IP validated the connection between ARL6IP1 and OLFM4, and overexpression partially counteracted the suppression of glycolysis and cell behavior resulting from knockdown.

Conclusion

is a critical regulator of BC progression, influencing glycolysis, mitochondrial function, and key cellular behaviors. Targeting the ARL6IP1-OLFM4 axis offers a promising therapeutic strategy for managing BC.

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2025-05-27
2025-09-14

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ARL6IP1 Inhibits Breast Cancer Tumor Progression by Targeting OLFM4 to Regulate Glycolysis
Bentham Science Publishers ; https://doi.org/10.2174/0113862073358595250211053816
/content/journals/cchts/10.2174/0113862073358595250211053816
/content/journals/cchts/10.2174/0113862073358595250211053816
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  • Article Type:     Research Article
Keywords: Breast cancer ; OLFM4 ; glycolysis ; ARL6P1 ; tumor progression

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