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J. Clin. Med. 2019, 8(1), 38; https://doi.org/10.3390/jcm8010038

FAK is Required for Tumor Metastasis-Related Fluid Microenvironment in Triple-Negative Breast Cancer

1
Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2
Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
3
Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
4
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6
National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan
7
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 807, Taiwan
8
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 807, Taiwan
9
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 807, Taiwan
Contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 9 November 2018 / Revised: 20 December 2018 / Accepted: 26 December 2018 / Published: 2 January 2019
(This article belongs to the Section Oncology)
Full-Text   |   PDF [2422 KB, uploaded 2 January 2019]   |  

Abstract

Cancer cell metastasis is the main cause of death in patients with cancer. Many studies have investigated the biochemical factors that affect metastasis; however, the role of physical factors such as fluid shear stress (FSS) in tumorigenesis and metastasis have been less investigated. Triple-negative breast cancer (TNBC) has a higher incidence of lymph node invasion and distant metastasis than other subtypes of breast cancer. In this study, we investigated the influence of FSS in regulating the malignant behavior of TNBC cells. Our data demonstrate that low FSS promotes cell migration, invasion, and drug resistance, while high FSS has the opposite results; additionally, we found that these phenomena were regulated through focal adhesion kinase (FAK). Using immunohistochemistry staining, we show that FAK levels correlate with the nodal stage and that FAK is a significant independent predictor of overall survival in patients. Altogether, these data implicate FAK as a fluid mechano-sensor that regulates the cell motility induced by FSS and provide a strong rationale for cancer treatments that combine the use of anti-cancer drugs and strategies to modulate tumor interstitial fluid flow. View Full-Text
Keywords: Fluid shear stress; focal adhesion kinase; triple-negative breast cancer; cell migration; drug sensitivity Fluid shear stress; focal adhesion kinase; triple-negative breast cancer; cell migration; drug sensitivity
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Pan, M.-R.; Hou, M.-F.; Ou-Yang, F.; Wu, C.-C.; Chang, S.-J.; Hung, W.-C.; Yip, H.-K.; Luo, C.-W. FAK is Required for Tumor Metastasis-Related Fluid Microenvironment in Triple-Negative Breast Cancer. J. Clin. Med. 2019, 8, 38.

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