Extracellular Vesicles Derived from SIPA1<sup>high</sup> 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
Affiliations
Lingyun Feng
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Jun Weng
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Chenguang Yao
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Ruyuan Wang
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Ning Wang
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Yilei Zhang
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
Yoshimasa Tanaka
Center for Medical Innovation, Nagasaki University, 1-7-1, Sakamoto, Nagasaki 852-8588, Japan
Li Su
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
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, SIPA1high breast cancer can enhance macrophage infiltration through EVs enriched with myosin-9, which might aggravate the malignancy of breast cancer.
