PUBLICATION
PAK4 suppresses PDZ-RhoGEF activity to drive invadopodia maturation in melanoma cells
- Authors
- Nicholas, N.S., Pipili, A., Lesjak, M.S., Ameer-Beg, S.M., Geh, J.L., Healy, C., MacKenzie Ross, A.D., Parsons, M., Nestle, F.O., Lacy, K.E., Wells, C.M.
- ID
- ZDB-PUB-180224-7
- Date
- 2016
- Source
- Oncotarget 7: 70881-70897 (Journal)
- Registered Authors
- Keywords
- PAK, PDZ-RhoGEF, RhoA, invadopodia, melanoma
- MeSH Terms
-
- Actins
- Animals
- Cell Line, Tumor
- Fluorescent Antibody Technique
- HEK293 Cells
- Humans
- Melanoma/pathology*
- Neoplasm Invasiveness/pathology
- Podosomes/pathology*
- Protein Isoforms/metabolism
- RNA Interference
- RNA, Small Interfering/metabolism
- Rho Guanine Nucleotide Exchange Factors/metabolism*
- Signal Transduction
- Skin Neoplasms/pathology*
- Zebrafish
- p21-Activated Kinases/genetics
- p21-Activated Kinases/metabolism*
- PubMed
- 27765920 Full text @ Oncotarget
Citation
Nicholas, N.S., Pipili, A., Lesjak, M.S., Ameer-Beg, S.M., Geh, J.L., Healy, C., MacKenzie Ross, A.D., Parsons, M., Nestle, F.O., Lacy, K.E., Wells, C.M. (2016) PAK4 suppresses PDZ-RhoGEF activity to drive invadopodia maturation in melanoma cells. Oncotarget. 7:70881-70897.
Abstract
Cancer cells are thought to use actin rich invadopodia to facilitate matrix degradation. Formation and maturation of invadopodia requires the co-ordained activity of Rho-GTPases, however the molecular mechanisms that underlie the invadopodia lifecycle are not fully elucidated. Previous work has suggested a formation and disassembly role for Rho family effector p-21 activated kinase 1 (PAK1) however, related family member PAK4 has not been explored. Systematic analysis of isoform specific depletion using in vitro and in vivo invasion assays revealed there are differential invadopodia-associated functions. We consolidated a role for PAK1 in the invadopodia formation phase and identified PAK4 as a novel invadopodia protein that is required for successful maturation. Furthermore, we find that PAK4 (but not PAK1) mediates invadopodia maturation likely via inhibition of PDZ-RhoGEF. Our work points to an essential role for both PAKs during melanoma invasion but provides a significant advance in our understanding of differential PAK function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping