Increased SLC7A3 Expression inhibits Tumor Cell Proliferation and Predicts a Favorable Prognosis in Breast Cancer

Lifang He; Yue Xu; Jiediao Lin; Stanley Lin; Yukun Cui

doi:10.2174/0115748928279007231130070056

Increased SLC7A3 Expression inhibits Tumor Cell Proliferation and Predicts a Favorable Prognosis in Breast Cancer

Recent Pat Anticancer Drug Discov. 2024 Jan 8. doi: 10.2174/0115748928279007231130070056. Online ahead of print.

Authors

Lifang He^{1

2}, Yue Xu¹, Jiediao Lin¹, Stanley Lin^{1

3}, Yukun Cui¹

Affiliations

¹ Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, 515000, China.
² Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, 515000, China.
³ Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong Province, 515000, China.

PMID: 38204267
DOI: 10.2174/0115748928279007231130070056

Abstract

Background: Arginine plays significant and contrasting roles in breast cancer growth and survival. However, the factors governing arginine balance remain poorly characterized.

Objective: We aimed to identify the molecule that governs arginine metabolism in breast cancer and to elucidate its significance.

Methods: We analyzed the correlation between the expression of solute carrier family 7 member 3 (SLC7A3), the major arginine transporter, and breast cancer survival in various databases, including GEPIA, UALCAN, Metascape, String, Oncomine, KM-plotter, CBioPortal and Prognosis. Additionally, we validated our findings through bioinformatic analyses and experimental investigations, including colony formation, wound healing, transwell, and mammosphere formation assays.

Results: Our analysis revealed a significant reduction in SLC7A3 expression in all breast cancer subtypes compared to adjacent breast tissues. Kaplan-Meier survival analyses demonstrated that high SLC7A3 expression was positively associated with decreased nodal metastasis (HR=0.70, 95% CI [0.55, 0.89]), ER positivity (HR=0.79, 95% CI [0.65, 0.95]), and HER2 negativity (HR=0.69, 95% CI [0.58, 0.82]), and increased recurrence-free survival. Moreover, low SLC7A3 expression predicted poor prognosis in breast cancer patients for overall survival. Additionally, the knockdown of SLC7A3 in MCF-7 and MDA-MB-231 cells resulted in increased cell proliferation and invasion in vitro.

Conclusion: Our findings indicate a downregulation of SLC7A3 expression in breast cancer tissues compared to adjacent breast tissues. High SLC7A3 expression could serve as a prognostic indicator for favorable outcomes in breast cancer patients due to its inhibitory effects on breast cancer cell proliferation and invasion.

Keywords: SLC7A3; arginine; breast cancer; cell proliferation; prognosis.; tumor suppressor.