Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer

Fang Yang,Jin Xiang,Ke Su,Shan Zhu,Pengchao Hu,Jingwei Zhang,Lei Wei,Changchun Kuang,Xiaolan Wang,Qingmin Xiang

doi:10.18632/oncotarget.9968

Abstract

Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent.

Highlights

Breast cancer is the most common malignancy in women worldwide and its mortality rate is second to cervical cancer in developing countries [1]
Strong expression (+++) of vasodilator-stimulated phosphoprotein (VASP) was present in 25.0% (2/8) of Luminal A, 10.5% (2/19) of luminal B, 71.4% (5/7) of basal-like, and 71.4% (5/7) of HER-2 overexpression samples (Table 1)
Previous studies have revealed many potential biomarkers associated with poor prognosis in basal-like breast cancer, including basal cytokeratins (CK5/6, CK14, CK17), epidermal growth factor receptor (EGFR), c-kit, P63, P-cadherin and FOXC1, currently, there are no targeted treatments

Summary

Introduction

Breast cancer is the most common malignancy in women worldwide and its mortality rate is second to cervical cancer in developing countries [1]. Over the past 30 years, the incidence and mortality of breast cancer have been increasing, with a rate that is second only to lung cancer [1]. Luminal A is the most common type of cancer (~46% of cases), followed by basal-like (~28.8%), luminal B (~14.7%) and HER2 overexpression (~10.4%)[4, 5]. These four molecular subtypes of breast cancer differ in phenotype, response to drugs, and survival rates, requiring different treatments. While the luminal and HER-2 overexpression types of breast cancer are responsive to targeted treatments, systemic chemotherapy is still the main form of routine www.impactjournals.com/oncotarget treatment for basal-like breast cancer [9], which is characterized by poor prognosis [10]

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