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Title: P21-activated kinase 1 stimulates colon cancer cell growth and migration/invasion via ERK- and AKT-dependent pathways.
Austin Authors: Huynh, Nhi;Liu, Kevin H;Baldwin, Graham S;He, Hong 
Affiliation: Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia 3084, Australia
Issue Date: 1-Jun-2010
Publication information: Biochimica Et Biophysica Acta 2010; 1803(9): 1106-13
Abstract: The p21-activated kinase (PAK) family of serine/threonine kinases plays an important role in cell proliferation, survival and motility, as well as in cell transformation and tumor progression. PAK1 promotes transformation through facilitating the ERK/MAPK pathway and enhances cell migration and survival by stimulating AKT. PAK1 expression increases with the progression of colorectal cancer (CRC). In this study, we have investigated the importance of PAK1 in the biology of colon cancer cells. Reduction of PAK1 expression decreased the activities of ERK and AKT leading to decreased cell proliferation, migration/invasion, and survival. Dual inhibition of ERK and AKT suppressed these cellular processes to levels comparable to those achieved by reduction of PAK1 expression, whereas inactivation of either the ERK or AKT pathway alone partially inhibited cell migration/invasion and survival and had no effect on proliferation. We conclude that PAK1 stimulates colon cancer cell proliferation, migration/invasion, and survival via ERK- and AKT-dependent pathways. These findings establish the central importance of PAK1 in CRC signal transduction and clarify the mechanism by which PAK1 regulates CRC growth and migration. Instead of simultaneously inhibiting both ERK and AKT, the PAK1 convergence point could be an alternative target for CRC therapy.
Gov't Doc #: 20595063
DOI: 10.1016/j.bbamcr.2010.05.007
Journal: Biochimica et biophysica acta
Type: Journal Article
Subjects: Carcinoma.genetics.metabolism.pathology
Cell Movement.drug effects.genetics.physiology
Cell Proliferation.drug effects
Cell Survival.drug effects.genetics
Colonic Neoplasms.genetics.metabolism.pathology
Extracellular Signal-Regulated MAP Kinases.metabolism.physiology
HCT116 Cells
MAP Kinase Signaling System.drug effects.physiology
Models, Biological
Neoplasm Invasiveness
Oncogene Protein v-akt.metabolism.physiology
RNA, Small Interfering.pharmacology
Signal Transduction.drug effects.genetics.physiology
Tumor Cells, Cultured
p21-Activated Kinases.antagonists & inhibitors.genetics.physiology
Appears in Collections:Journal articles

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