FAK is required for tumor metastasis-related fluid microenvironment in triple-negative breast cancer

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.