Overexpression of vimentin contributes to prostate cancer invasion and metastasis via src regulation.
A significant proportion of prostate cancer patients treated with curative intent develop advanced disease. At a fundamental biological level, very little is known about what makes the disease aggressive and metastatic. Observational pathology reports and experimental data suggest that an epithelial-mesenchymal transition (EMT) is involved in prostate cancer invasiveness. The mechanism by which vimentin promotes prostate cancer cell invasion and metastasis was examined. The highly metastatic human prostate epithelial cell line PC-3M-1E8 (1E8-H) and the low metastatic line PC-3M-2B4 (2B4-L) were used for comparative proteomic analysis by two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/time of flight mass spectrometry (MALDI-TOF-MS). A transwell assay was performed to test cell migration and invasion and immunoblotting was used to analyze the relative expression of proteins. High vimentin expression was detected in 1E8-H compared to 2B4-L cells. Down-regulation of vimentin in 1E8-H by antisense-vimentin transfection led to a significant inhibition of invasiveness, and selective stimulation of vimentin activity in 2B4-L by delivery of recombinant vimentin promoted cell invasiveness. Vimentin activity was associated with C-src, beta-catenin and E-cadherin expression. PP2, a specific inhibitor of src family kinases, reduced phospho-beta-catenin expression and induce E-cadherin expression. Vimentin promotes tumor cell invasiveness and the targeting of vimentin/C-src may be a promising strategy for preventing or blocking prostate cancer metastasis.
Wei
Juncheng
J
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Xu
Gang
G
Wu
Mingfu
M
Zhang
Yongtao
Y
Li
Qiong
Q
Liu
Ping
P
Zhu
Tao
T
Song
Anping
A
Zhao
Liangpin
L
Han
Zhiqiang
Z
Chen
Gang
G
Wang
Shixuan
S
Meng
Li
L
Zhou
Jianfeng
J
Lu
Yunping
Y
Wang
Shixuan
S
Ma
Ding
D
D015153:Blotting, Western; D000081247:CSK Tyrosine-Protein Kinase; D015820:Cadherins / Q000378:metabolism; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D040901:Proteomics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection; D014746:Vimentin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D019061:src-Family Kinases
D015820:Cadherins; D011518:Proto-Oncogene Proteins; D014746:Vimentin; D051176:beta Catenin; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human