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• W2123453804 abstract "The FERM domain containing protein Kindlin-3 has been recognized as a major regulator of integrin function in hematopoietic cells, but its role in neoplasia is totally unknown. We have examined the relationship between Kindlin-3 and breast cancer in mouse models and human tissues. Human breast tumors showed a ~7-fold elevation in Kindlin-3 mRNA compared with nonneoplastic tissue by quantitative polymerase chain reaction. Kindlin-3 overexpression in a breast cancer cell line increased primary tumor growth and lung metastasis by 2.5- and 3-fold, respectively, when implanted into mice compared with cells expressing vector alone. Mechanistically, the Kindlin-3-overexpressing cells displayed a 2.2-fold increase in vascular endothelial growth factor (VEGF) secretion and enhanced β1 integrin activation. Increased VEGF secretion resulted from enhanced production of Twist, a transcription factor that promotes tumor angiogenesis. Knockdown of Twist diminished VEGF production, and knockdown of β1 integrins diminished Twist and VEGF production by Kindlin-3-overexpressing cells, while nontargeting small interfering RNA had no effect on expression of these gene products. Thus, Kindlin-3 influences breast cancer progression by influencing the crosstalk between β1 integrins and Twist to increase VEGF production. This signaling cascade enhances breast cancer cell invasion and tumor angiogenesis and metastasis.—Sossey-Alaoui, K., Pluskota, E., Davuluri, G., Bialkowska, K., Das, M., Szpak, D., Lindner, D. J., Downs-Kelly, E., Thompson, C. L., Plow, E. F. Kindlin-3 enhances breast cancer progression and metastasis by activating Twist-mediated angiogenesis. FASEB J. 28, 2260–2271 (2014). www.fasebj.org" @default.
• W2123453804 created "2016-06-24" @default.
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• W2123453804 date "2014-01-27" @default.
• W2123453804 modified "2023-10-14" @default.
• W2123453804 title "Kindlin‐3 enhances breast cancer progression and metastasis by activating Twist‐mediated angiogenesis" @default.
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• W2123453804 doi "https://doi.org/10.1096/fj.13-244004" @default.
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