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SCARA5 plays a critical role in the progression and metastasis of breast cancer by inactivating the ERK1/2, STAT3, and AKT signaling pathways

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Abstract

Scavenger receptor class A member 5 (SCARA5) is a candidate anti-oncogene in several malignancies. However, whether SCARA5 is a suppressor gene in breast cancer and its role in breast cancer cell growth and metastasis remain to be determined. Here, we investigated the biological functions of SCARA5 in the progression and metastasis of breast cancer and explored the underlying mechanisms. A total of 65 breast cancer patients and three cell lines (ZR-75-30, MCF-7, and MDA-MB-231) were analyzed in the study. RT-qPCR, western blotting, and immunohistochemistry were used to detect mRNA and protein expression, and lymphatic vessel density (LVD) and microvessel density (MVD). MTT, colony formation, TUNEL assays, invasion assays and Transwell assays, and flow cytometric analyses were used to evaluate the effect of SCARA5 on breast cancer cells. SCARA5 was significantly downregulated in breast cancer tissues and cells and significantly correlated with tumor size, histological grade, lymph node metastasis, pTNM stage, VEGF-A, VEGF-C, LVD, and MVD. SCARA5 overexpression significantly suppressed cell proliferation, colony formation, invasion, and migration, and induced G0/G1 arrest and apoptosis of ZR-75-30 cells. SCARA5 decreased the phosphorylation of ERK1/2, AKT, and STAT3, and downregulated downstream signaling effectors, including MMP-2, 3, and 9, VEGF-A, VEGF-C, Bax, Cyclin B1, Cyclin D1, and Cyclin E1, and upregulated E-cadherin, Bcl-2, and caspase 3. SCARA5 is associated with multiple signaling pathways and plays a critical role in the progression and metastasis of breast cancer. The present results provide the first evidence that SCARA5 inhibits lymphangiogenesis by downregulating VEGF-C, thereby inhibiting breast cancer lymphatic metastasis.

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Funding

This study was funded by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry and National Natural Science Foundation of China (Grant No. 81372838).

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Author notes

  1. Kai You and Fei Su have contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People’s Republic of China

    Kai You, Lihua Liu, Xiaohong Lv, Yafang Zhang & Baoquan Liu

  2. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, People’s Republic of China

    Fei Su

  3. Department of General Surgery, The Second Clinical Hospital, Harbin Medical University, Harbin, 150081, People’s Republic of China

    Jianguo Zhang

Authors
  1. Kai You
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  2. Fei Su
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  3. Lihua Liu
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  4. Xiaohong Lv
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  5. Jianguo Zhang
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  6. Yafang Zhang
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  7. Baoquan Liu
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Correspondence to Yafang Zhang or Baoquan Liu.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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You, K., Su, F., Liu, L. et al. SCARA5 plays a critical role in the progression and metastasis of breast cancer by inactivating the ERK1/2, STAT3, and AKT signaling pathways. Mol Cell Biochem 435, 47–58 (2017). https://doi.org/10.1007/s11010-017-3055-4

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  • DOI: https://doi.org/10.1007/s11010-017-3055-4

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