LaminA/C Protein is Overexpressed in Tissue-Invading Prostate Cancer and Promotes Prostate Cancer Cell Growth, Migration and Invasion through the PI3K/AKT/PTEN Pathway
Menée sur des lignées cellulaires de cancer de la prostate, cette étude suggère que, en modulant la voie de signalisation PI3K/AKT/PTEN, la protéine de membrane nucléaire Lamin A/C joue un rôle dans le processus invasif
Prostate cancer remains the second most common cause of cancer-related death in Western countries. A previous proteomics study suggested the nuclear membrane protein laminA/C to be a maker to discriminate low and high Gleason score tumors and to identify high risk cancers. To characterize its function in prostate cancer cells, we performed a detailed expression analysis in prostate cancer tissue and explored the consequences of down or up-regulation of laminA/C in prostate cancer cells. Our results confirm an increased laminA/C protein expression in high risk cancers and show association of expression with tumor cell formations at the invasion fronts of tumors and in invasion “spearheading” tumor cell clusters. In the prostate tumor cell lines LNCaP, DU145, and PC3 shRNA knockdown or overexpression of laminA/C resulted in inhibition or stimulation, respectively, of cell growth, colony formation, migration and invasion. Further mechanism studies suggested that the laminA/C-related malignant behavior is regulated through modulation of the phosphoinositide 3-kinase (PI3K)/AKT/PTEN signaling pathway. Western blot results indicated that knockdown or overexpression of laminA/C decreased or increased, respectively, protein levels of the PI3K subunits p110 and p85 in all 3 cell lines; phosphor-AKT in the PTEN negative cell lines LNCaP and PC3, and, increased or decreased, respectively, PTEN protein levels in PTEN positive DU145 cells. Together, our data suggest that laminA/C proteins are positively involved in malignant behavior of prostate cancer cells through the PI3K/AKT/PTEN pathway. LaminA/C may represent a new oncogenic factor and a novel therapeutic target for prostate cancer.
http://carcin.oxfordjournals.org/content/early/2012/02/01/carcin.bgs022.abstract 2012