Lamin A/C protein is overexpressed in tissue-invading prostate cancer and promotes prostate cancer cell growth, migration and invasion through the PI3K/AKT/PTEN pathway.
Prostate cancer (PC) remains the second most common cause of cancer-related death in Western countries. A previous proteomics study suggested that the nuclear membrane protein lamin A/C to be a maker to discriminate low- and high-Gleason score tumors and to identify high-risk cancers. To characterize its function in PC cells, we performed a detailed expression analysis in PC tissue and explored the consequences of down or upregulation of lamin A/C in PC cells. Our results confirm an increased lamin A/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 small hairpin RNA knockdown or overexpression of lamin A/C resulted in inhibition or stimulation, respectively, of cell growth, colony formation, migration and invasion. Further mechanism studies suggested that the lamin A/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 lamin A/C decreased or increased, respectively, protein levels of the PI3K subunits p110 and p85 in all three 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 lamin A/C proteins are positively involved in malignant behavior of PC cells through the PI3K/AKT/PTEN pathway. Lamin A/C may represent a new oncogenic factor and a novel therapeutic target for PC.
Department of Biochemistry and Molecular Biology, Capital Medical University, No 10 Xitoutiao, You An Men, Beijing 100069, PR China.
Lu
L
Kong
Georg
G
Schäfer
Huajie
H
Bu
Yong
Y
Zhang
Yuxiang
Y
Zhang
Helmut
H
Klocker
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D034904:Lamin Type A / Q000378:metabolism*; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
D034904:Lamin Type A; C440308:lamin C; D019870:1-Phosphatidylinositol 4-Kinase; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human