PKN3 is required for malignant prostate cell growth downstream of activated PI 3-kinase
- 29 July 2004
- journal article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 23 (16), 3303-3313
- https://doi.org/10.1038/sj.emboj.7600345
Abstract
Chronic activation of the phosphoinositide 3‐kinase (PI3K)/PTEN signal transduction pathway contributes to metastatic cell growth, but up to now effectors mediating this response are poorly defined. By simulating chronic activation of PI3K signaling experimentally, combined with three‐dimensional (3D) culture conditions and gene expression profiling, we aimed to identify novel effectors that contribute to malignant cell growth. Using this approach we identified and validated PKN3, a barely characterized protein kinase C‐related molecule, as a novel effector mediating malignant cell growth downstream of activated PI3K. PKN3 is required for invasive prostate cell growth as assessed by 3D cell culture assays and in an orthotopic mouse tumor model by inducible expression of short hairpin RNA (shRNA). We demonstrate that PKN3 is regulated by PI3K at both the expression level and the catalytic activity level. Therefore, PKN3 might represent a preferred target for therapeutic intervention in cancers that lack tumor suppressor PTEN function or depend on chronic activation of PI3K.Keywords
This publication has 39 references indexed in Scilit:
- Identification of novel effectors of invasive cell growth downstream of phosphoinositide 3-kinaseBiochemical Society Transactions, 2004
- Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasisNature Reviews Molecular Cell Biology, 2003
- Phosphoinositide 3-kinase signalling – which way to target?Trends in Pharmacological Sciences, 2003
- Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigmBiochemical Journal, 2003
- Compensation mechanism in tumor cell migrationThe Journal of cell biology, 2003
- The Protein Kinase Complement of the Human GenomeScience, 2002
- GeneBlocs Are Powerful Tools to Study and Delineate Signal Transduction Processes That Regulate Cell Growth and TransformationAntisense and Nucleic Acid Drug Development, 2002
- Rho GTPase Control of Protein Kinase C-related Protein Kinase Activation by 3-Phosphoinositide-dependent Protein KinasePublished by Elsevier BV ,2000
- Identification and Characterization of PKNβ, a Novel Isoform of Protein Kinase PKN: Expression and Arachidonic Acid Dependency Are Different from Those of PKNαBiochemical and Biophysical Research Communications, 1999
- Metastatic Model for Human Prostate Cancer Using Orthotopic Implantation in Nude MiceJNCI Journal of the National Cancer Institute, 1992