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Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis

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Abstract

Src family kinases (SFKs) are signaling enzymes that have long been recognized to regulate critical cellular processes such as proliferation, survival, migration, and metastasis. Recently, considerable work has elucidated mechanisms by which SFKs regulate normal and pathologic processes in vascular biology, including endothelial cell proliferation and permeability. Further, when inappropriately activated, SFKs promote pathologic inflammatory processes and tumor metastasis, in part through their effects on the regulation of endothelial monolayer permeability. In this review, we discuss the roles of aberrantly activated SFKs in mediating endothelial permeability in the context of inflammatory states and tumor cell metastasis. We further summarize recent efforts to translate Src-specific inhibitors into therapy for systemic inflammatory conditions and numerous solid organ cancers.

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Authors and Affiliations

  1. Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box no. 173, Houston, TX, 77030–4009, USA

    M. P. Kim, S. I. Park, S. Kopetz & G. E. Gallick

  2. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, USA

    M. P. Kim

  3. Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, USA

    S. Kopetz

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Correspondence to G. E. Gallick.

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The authors’ own research was supported in part by NIH U54 CA 090810 and P20 CA101936 (G.E.G) and NIH T32 CA 09599 (M.P.K.)

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Kim, M.P., Park, S.I., Kopetz, S. et al. Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis. Cell Tissue Res 335, 249–259 (2009). https://doi.org/10.1007/s00441-008-0682-9

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