The function of Cav-1 in MDA-MB-231 breast cancer cell migration and invasion induced by ectopic ATP5B

Xinjie Dong,Wei Li,Yilei Li,Wenzhe Kang,Lijuan Zhou,Ziyi Xing,Wenyi Wu,Rong Tang

doi:10.1007/s12032-021-01519-5

Abstract

Ectopic ATP5B, which is located in a unique type of lipid raft caveolar structure, can be upregulated by cholesterol loading. As the structural component of caveolae, Cav-1 is a molecular hub that is involved in transmembrane signaling. In a previous study, the ATP5B-specific binding peptide B04 was shown to inhibit the migration and invasion of prostate cancer cells, and the expression of ATP5B on the plasma membrane of MDA-MB-231 cells was confirmed. The present study investigated the effect of ectopic ATP5B on the migration and invasion of MDA-MB-231 cells and examined the involvement of Cav-1. Cholesterol loading increased the level of ectopic ATP5B and promoted cell migration and invasion. These effects were blocked by B04. Ectopic ATP5B was physically colocalized with Cav-1, as demonstrated by double immunofluorescence staining and coimmunoprecipitation. After Cav-1 knockdown, the migration and invasion abilities of MDA-MB-231 cells were significantly decreased, suggesting that Cav-1 influences the function of ectopic ATP5B. Furthermore, these effects were not reversed after treatment with cholesterol. We concluded that Cav-1 may participate in MDA-MB-231 cell migration and invasion induced by binding to ectopic ATP5B.

Highlights

As the most common malignancy in women, breast cancer accounts for 18% of female cancer cases [1]
We investigated the potential role of ectopic ATP5B in the migration and invasion of MDA-MB-231 cells
The numbers of migrated and invaded cells treated with B04 before exposure to cholesterol were not different from those in the group treated with B04 alone. These results suggest that cholesterol loading promotes cell migration and invasion by inducing ectopic expression of ATP5B

Summary

Introduction

As the most common malignancy in women, breast cancer accounts for 18% of female cancer cases [1]. Distant metastasis in patients diagnosed with early breast cancer accounts for only 5–10% of all cases, the risk of metastasis remains quite high after primary surgical resection and Adenosine triphosphate synthase beta subunit (ATP5B) is the β subunit of F1F0-ATP synthase and contains the catalytic site for ATP synthesis as well as hydrolysis [4]. As a subunit of F 1F0-ATP synthase, ATP5B was once thought to be strictly located at the inner side of the mitochondrial membrane. More recent studies have revealed its ectopic expression on the outer surface of the plasma membrane of highly metabolic cells, where it is called ectopic ATP5B [5]. Many of the examined markers were of greater or lesser clinical significance [15–18]

Methods

Results

Conclusion