p21-activated kinases in human cancer

@article{Vadlamudi2004p21activatedKI,
  title={p21-activated kinases in human cancer},
  author={Ratna K. Vadlamudi and Rakesh Kumar},
  journal={Cancer and Metastasis Reviews},
  year={2004},
  volume={22},
  pages={385-393}
}
A balance between proliferation, differentiation, migration and death of cells is critical for the normal development of an organism. Perturbations of this balance can contribute to cancer development. The p21-activated serine/threonine kinases (Paks) play an important role in a variety of cellular functions including cell morphogenesis, motility, survival, angiogenesis, and mitosis. Paks were initially identified as an effector molecules of RHO GTPases; however, recent evidence that they can… 

Development of p21 activated kinase-targeted multikinase inhibitors that inhibit thyroid cancer cell migration.

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Nuclear Localization and Chromatin Targets of p21-activated Kinase 1*

Investigations provide proof-of-principle evidence that Pak1 could influence the expression of its putative chromatin targets in both a positive and a negative manner, opening new avenues to further the search for nuclear Pak1 functions and identify putative Pak1-interacting nuclear proteins.

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Group I p21-activated kinases regulate thyroid cancer cell migration and are overexpressed and activated in thyroid cancer invasion.

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Emodin inhibits tumor cell migration through suppression of the phosphatidylinositol 3-kinase-Cdc42/Rac1 pathway

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RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo

RACK1 is an independent prognosis-related factor and promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo and can be inhibited by the addition of Rho-kinase inhibitor.
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References

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The current knowledge of the Paks family with respect to emerging cellular functions and possible contributions to cancer is summarized.

Requirement for PAK4 in the Anchorage-independent Growth of Human Cancer Cell Lines*

It is demonstrated that PAK4 is frequently overexpressed in human tumor cell lines of various tissue origins and identified serine (Ser-474) as the likely autophosphorylation site in the kinase domain of PAK 4 in vivo, and suggested thatPAK4 activity is required for Ras-driven, anchorage-independent growth.

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It is demonstrated that overexpression of a kinase dead K299R PAK1 mutant leads to suppression of motile phenotypes as well as invasiveness of cells both in the absence or presence of exogenous heregulin-β1, and downstream pathways have a role in the development and maintenance of invasive phenotypes in breast cancer cells.

Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway.

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p21-Activated Kinase 1 (Pak1) Regulates Cell Motility in Mammalian Fibroblasts

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A Role for P21-Activated Kinase in Endothelial Cell Migration

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Heregulin Regulates Cytoskeletal Reorganization and Cell Migration through the p21-activated Kinase-1 via Phosphatidylinositol-3 Kinase*

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