Extracellular Vesicles Derived from SIPA1high Breast Cancer Cells Enhance Macrophage Infiltration and Cancer Metastasis through Myosin-9

Lingyun Feng; Jun Weng; Chenguang Yao; Ruyuan Wang; Ning Wang; Yilei Zhang; Yoshimasa Tanaka; Li Su

doi:10.3390/biology11040543

Extracellular Vesicles Derived from SIPA1^high Breast Cancer Cells Enhance Macrophage Infiltration and Cancer Metastasis through Myosin-9

Biology (Basel). 2022 Mar 31;11(4):543. doi: 10.3390/biology11040543.

Authors

Lingyun Feng¹, Jun Weng¹, Chenguang Yao¹, Ruyuan Wang¹, Ning Wang¹, Yilei Zhang², Yoshimasa Tanaka³, Li Su¹

Affiliations

¹ Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
² The Institute of Molecular and Translational Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
³ Center for Medical Innovation, Nagasaki University, 1-7-1, Sakamoto, Nagasaki 852-8588, Japan.

Abstract

Tumour cell metastasis can be genetically regulated by proteins contained in cancer cell-derived extracellular vesicles (EVs) released to the tumour microenvironment. Here, we found that the number of infiltrated macrophages was positively correlated with the expression of signal-induced proliferation-associated 1 (SIPA1) in invasive breast ductal carcinoma tissues and MDA-MB-231 xenograft tumours. EVs derived from MDA-MB-231 cells (231-EVs) significantly enhanced macrophage migration, compared with that from SIPA1-knockdown MDA-MB-231 cells (231/si-EVs) both in vitro and in vivo. We revealed that SIPA1 promoted the transcription of MYH9, which encodes myosin-9, and up-regulated the expression level of myosin-9 in breast cancer cells and their EVs. We also found that blocking myosin-9 by either down-regulating SIPA1 expression or blebbistatin treatment led to the suppression of macrophage infiltration. Survival analysis showed that breast cancer patients with high expression of SIPA1 and MYH9 molecules had worse relapse-free survival (p = 0.028). In summary, SIPA1^high breast cancer can enhance macrophage infiltration through EVs enriched with myosin-9, which might aggravate the malignancy of breast cancer.

Keywords: SIPA1; breast cancer; extracellular vesicles; macrophage; myosin-9.

Abstract

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