p-21 activated 6 (PAK6), first identified as interacting with the androgen receptor (AR), is over-expressed in multiple cancer tissues and has been linked to the progression of prostate cancer, however little is known about PAK6 function in the absence of AR signaling. We report here that PAK6 is specifically required for carcinoma cell-cell dissociation downstream of hepatocyte growth factor (HGF) for both DU145 prostate cancer and HT29 colon cancer cells. Moreover, PAK6 overexpression can drive cells to escape from adhesive colonies in the absence of stimulation. We have localized PAK6 to cell-cell junctions and have detected a direct interaction between the kinase domain of PAK6 and the junctional protein IQGAP1. Co-expression of IQGAP1 and PAK6 increases cell colony escape and leads to elevated PAK6 activation. Further studies have identified a PAK6/E-cadherin/IQGAP1 complex downstream of HGF. Moreover, we find that β-catenin is also localized with PAK6 in cell-cell junctions and is a novel PAK6 substrate. We propose a unique role for PAK6, independent of AR signaling, where PAK6 drives junction disassembly during HGF-driven cell-cell dissociation via an IQGAP1/E-cadherin complex that leads to the phosphorylation of β-catenin and the disruption of cell-cell adhesions.
Pubmed ID: 24352566 RIS Download
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An antibody supplier for the purposes of life science and biomedical research. This company has a wide variety of immunological reagents that focus on areas of research such as cancer, cell biology, epigenetics, immunology and infectious diseases.
View all literature mentionsA live cell imaging software that allows for control of iXon EMCCD and sCMOS cameras in synchronized combination with a number of additional imaging hardware devices. iQ can be used to run experiments to investigate dynamic processes in both single cells and multicellular systems, image fixed samples, and generate 3 dimensional image volumes for analysis.
View all literature mentionsCell line HT-29 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Capan-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DU145 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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