Journal of Breast Cancer

Korean Breast Cancer Society (한국유방암학회)
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Deficiency of Follistatin-Like Protein 1 Accelerates the Growth of Breast Cancer Cells at Lung Metastatic Sites

  • Zhang, Ying (Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University) ;
  • Xu, Xiaozhou (Department of Breast Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences) ;
  • Yang, Ying (Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University) ;
  • Ma, Jie (Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University) ;
  • Wang, Lulu (Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University) ;
  • Meng, Xiangzhi (Department of Breast Surgery, Cancer Hospital of Huanxing Chaoyang District Beijing) ;
  • Chen, Bing (Department of Clinical Laboratory, Cancer Hospital of Huanxing Chaoyang District Beijing) ;
  • Qin, Ling (Department of Breast Surgery, Cancer Hospital of Huanxing Chaoyang District Beijing) ;
  • Lu, Tao (Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University) ;
  • Gao, Yan (Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University)
  • Received : 2018.03.02
  • Accepted : 2018.06.01
  • Published : 2018.09.30
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Abstract

Purpose: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been shown to play a role in various types of cancer. However, the clinical significance and function of FSTL1 in breast cancer have not been reported. We investigated the role of FSTL1 in breast cancer in this study. Methods: Enzyme-linked immunosorbent assays, western blot analysis, and reverse transcription polymerase chain reaction were used to monitor the expression of FSTL1 in breast cancer tissue and in serum samples from breast cancer patients. We employed a 4T1 breast cancer model and $Fstl1^{+/-}$ mice for in vivo studies. Hematoxylin and eosin staining, western blot analysis, and RNA sequencing were used to analyze the effect of FSTL1 on primary tumor growth and lung metastasis. Results: We demonstrated that the expression of FSTL1 is reduced in both the breast cancer tissue and the serum of breast cancer patients. We showed that reduced levels of FSTL1 in serum correlate with elevated expression of Ki-67 and epidermal growth factor receptor (EGFR) in cancer tissues. Moreover, lowered expression of FSTL1 was associated with decreased survival in breast cancer patients. Experiments on the $Fstl1^{+/-}$ mouse model established that FSTL1 deficiency had no effect on primary tumor growth, but increased the lung metastases of breast cancer cells, resulting in reduced survival of tumor-bearing mice. RNA sequencing found significantly reduced expression of Egln3 and increased expression of EGFR in $Fstl1^{+/-}$ mice. Thus, our results suggest that FSTL1 may affect the expression of EGFR through Egln3, inhibiting the proliferation of breast cancer cells at lung metastatic sites. Conclusion: In conclusion, we suggest a suppressor role of FSTL1 in breast cancer lung metastasis. Furthermore, FSTL1 may represent a potential prognostic biomarker and a candidate therapeutic target in breast cancer patients.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation of China

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