FAK Regulates VEGFR2 Expression and Promotes Angiogenesis in Triple-Negative Breast Cancer

Jun-Ping Shiau; Cheng-Che Wu; Shu-Jyuan Chang; Mei-Ren Pan; Wangta Liu; Fu Ou-Yang; Fang-Ming Chen; Ming-Feng Hou; Shen-Liang Shih; Chi-Wen Luo

doi:10.3390/biomedicines9121789

journal article Open Access Nov 29, 2021

FAK Regulates VEGFR2 Expression and Promotes Angiogenesis in Triple-Negative Breast Cancer

Jun-Ping Shiau

Cheng-Che Wu Shu-Jyuan Chang

Mei-Ren Pan

Wangta Liu Fu Ou-Yang Fang-Ming Chen Ming-Feng Hou

Shen-Liang Shih

Chi-Wen Luo

Biomedicines Vol. 9 No. 12 pp. 1789 · MDPI AG

View at Publisher Save 10.3390/biomedicines9121789

Abstract

Triple-negative breast cancer (TNBC) remains a significant clinical challenge because of its high vascularity and metastatic and recurrent rates. Tumor angiogenesis is considered an important mediator in the regulation of tumor cell survival and metastasis in TNBC. Angiogenesis is induced by the binding of vascular endothelial growth factor to vascular endothelial growth factor receptor 2 (VEGFR2). Focal adhesion kinase (FAK) plays an important role in regulating various cell functions in normal and cancer cells. Previous studies have focused on investigating the function of endothelial FAK in tumor cell angiogenesis. However, the association between tumor FAK and VEGFR2 in tumor angiogenesis and the possible mechanisms of this remain unclear. In this study, we used a public database and human specimens to examine the association between FAK and VEGFR2. At the same time, we verified the association between FAK and VEGFR2 through several experimental methods, such as quantitative real-time polymerase chain reaction, Western blotting, and next-generation sequencing. In addition, we used the endothelial cell model, zebrafish, and xenograft animal models to investigate the role of FAK in TNBC angiogenesis. We found that FAK and VEGFR2 were positively correlated in patients with TNBC. VEGFR2 and several other angiogenesis-related genes were regulated by FAK. In addition, FAK regulated VEGFR2 and VEGF protein expression in TNBC cells. Functional assays showed that FAK knockdown inhibited endothelial tube formation and zebrafish angiogenesis. An animal model showed that FAK inhibitors could suppress tumor growth and tumor vascular formation. FAK promotes angiogenesis in TNBC cells by regulating VEGFR2 expression. Therefore, targeting FAK could be another antiangiogenic strategy for TNBC treatment.

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Details

Published: Nov 29, 2021
Vol/Issue: 9(12)
Pages: 1789
License: View

Authors

J

Jun-Ping Shiau

Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Department of Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 812, Taiwan

C

Cheng-Che Wu

Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

S

Shu-Jyuan Chang

Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

M

Mei-Ren Pan

Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan

W

Wangta Liu

Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

F

Fu Ou-Yang

Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

F

Fang-Ming Chen

Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

M

Ming-Feng Hou

Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan

S

Shen-Liang Shih

Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

C

Chi-Wen Luo

Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Cite This Article

Jun-Ping Shiau, Cheng-Che Wu, Shu-Jyuan Chang, et al. (2021). FAK Regulates VEGFR2 Expression and Promotes Angiogenesis in Triple-Negative Breast Cancer. Biomedicines, 9(12), 1789. https://doi.org/10.3390/biomedicines9121789

FAK Regulates VEGFR2 Expression and Promotes Angiogenesis in Triple-Negative Breast Cancer

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