Figure S4 from Kindlin-1 Promotes Pulmonary Breast Cancer Metastasis
journal contribution
posted on 2023-03-31, 01:24 authored by Sana Sarvi, Hitesh Patel, Jun Li, Georgia L. Dodd, Helen Creedon, Morwenna Muir, Jocelyn Ward, John C. Dawson, Martin Lee, Jayne Culley, Donald M. Salter, Andrew H. Sims, Adam Byron, Valerie G. BruntonFigure S4 shows supporting data that Kindlin-1 reduces integrin activation and lung colonization
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Cancer Research UK
European Research Council
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ARTICLE ABSTRACT
In breast cancer, increased expression of the cytoskeletal adaptor protein Kindlin-1 has been linked to increased risks of lung metastasis, but the functional basis is unknown. Here, we show that in a mouse model of polyomavirus middle T antigen–induced mammary tumorigenesis, loss of Kindlin-1 reduced early pulmonary arrest and later development of lung metastasis. This phenotype relied on the ability of Kindlin-1 to bind and activate β integrin heterodimers. Kindlin-1 loss reduced α4 integrin–mediated adhesion of mammary tumor cells to the adhesion molecule VCAM-1 on endothelial cells. Treating mice with an anti–VCAM-1 blocking antibody prevented early pulmonary arrest. Kindlin-1 loss also resulted in reduced secretion of several factors linked to metastatic spread, including the lung metastasis regulator tenascin-C, showing that Kindlin-1 regulated metastatic dissemination by an additional mechanism in the tumor microenvironment. Overall, our results show that Kindlin-1 contributes functionally to early pulmonary metastasis of breast cancer.Significance: These findings provide a mechanistic proof in mice that Kindin-1, an integrin-binding adaptor protein, is a critical mediator of early lung metastasis of breast cancer. Cancer Res; 78(6); 1484–96. ©2018 AACR.Usage metrics
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