[HTML][HTML] Activation of phosphoinositide 3-OH kinase by the α6β4 integrin promotes carcinoma invasion
LM Shaw, I Rabinovitz, HHF Wang, A Toker… - Cell, 1997 - cell.com
LM Shaw, I Rabinovitz, HHF Wang, A Toker, AM Mercurio
Cell, 1997•cell.comWe demonstrate that the α6β4 integrin promotes carcinoma invasion through a preferential
and localized targeting of phosphoinositide-3 OH kinase (PI3K) activity. Stable expression of
α6β4 increased carcinoma invasion in a PI3K-dependent manner, and transient expression
of a constitutively active PI3K increased invasion in the absence of α6β4. Ligation of α6β4
stimulated significantly more PI3K activity than ligation of β1 integrins, establishing
specificity among integrins for PI3K activation. α6β4-regulated PI3K activity was required for …
and localized targeting of phosphoinositide-3 OH kinase (PI3K) activity. Stable expression of
α6β4 increased carcinoma invasion in a PI3K-dependent manner, and transient expression
of a constitutively active PI3K increased invasion in the absence of α6β4. Ligation of α6β4
stimulated significantly more PI3K activity than ligation of β1 integrins, establishing
specificity among integrins for PI3K activation. α6β4-regulated PI3K activity was required for …
Abstract
We demonstrate that the α6β4 integrin promotes carcinoma invasion through a preferential and localized targeting of phosphoinositide-3 OH kinase (PI3K) activity. Stable expression of α6β4 increased carcinoma invasion in a PI3K-dependent manner, and transient expression of a constitutively active PI3K increased invasion in the absence of α6β4. Ligation of α6β4 stimulated significantly more PI3K activity than ligation of β1 integrins, establishing specificity among integrins for PI3K activation. α6β4-regulated PI3K activity was required for the formation of lamellae, dynamic sites of motility, in carcinoma cells. The small G protein Rac is required downstream of PI3K for invasion. These studies define a mechanism by which the α6β4 integrin promotes carcinoma invasion and invoke a novel function for PI3K signaling.
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