| First Author | Sarvi S | Year | 2018 |
| Journal | Cancer Res | Volume | 78 |
| Issue | 6 | Pages | 1484-1496 |
| PubMed ID | 29330144 | Mgi Jnum | J:258832 |
| Mgi Id | MGI:6144224 | Doi | 10.1158/0008-5472.CAN-17-1518 |
| Citation | Sarvi S, et al. (2018) Kindlin-1 Promotes Pulmonary Breast Cancer Metastasis. Cancer Res 78(6):1484-1496 |
| abstractText | 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 beta integrin heterodimers. Kindlin-1 loss reduced alpha4 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. (c)2018 AACR. |
