Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis.
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.
Kim
M P
MP
Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Box no. 173, Houston, TX 77030-4009, USA.
Park
S I
SI
Kopetz
S
S
Gallick
G E
GE
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D042783:Endothelial Cells / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D018836:Inflammation Mediators; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D019061:src-Family Kinases