Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo.
There are no effective therapies for disseminated prostate cancer. Constitutive activation of Stat5 in prostate cancer is associated with cancer lesions of high histological grade. We have shown that Stat5 is activated in 61% of distant metastases of clinical prostate cancer. Active Stat5 increased metastases formation of prostate cancer cells in nude mice by 11-fold in an experimental metastases assay. Active Stat5 promoted migration and invasion of prostate cancer cells, and induced rearrangement of the microtubule network. Active Stat5 expression was associated with decreased cell surface E-cadherin levels, while heterotypic adhesion of prostate cancer cells to endothelial cells was stimulated by active Stat5. Activation of Stat5 and Stat5-induced binding of prostate cancer cells to endothelial cells were decreased by inhibition of Src but not of Jak2. Gene expression profiling indicated that 21% of Stat5-regulated genes in prostate cancer cells were related to metastases, while 7.9% were related to proliferation and 3.9% to apoptosis. The work presented here provides the first evidence of Stat5 involvement in the induction of metastatic behavior of human prostate cancer cells in vitro and in vivo. Stat5 may provide a therapeutic target protein for disseminated prostate cancer.
Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Lei
L
Gu
Paraskevi
P
Vogiatzi
Martin
M
Puhr
Ayush
A
Dagvadorj
Jacqueline
J
Lutz
Amy
A
Ryder
Sankar
S
Addya
Paolo
P
Fortina
Carlton
C
Cooper
Benjamin
B
Leiby
Abhijit
A
Dasgupta
Terry
T
Hyslop
Lukas
L
Bubendorf
Kalle
K
Alanen
Tuomas
T
Mirtti
Marja T
MT
Nevalainen
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000378:metabolism
D034741:RNA, Small Interfering; D050799:STAT5 Transcription Factor; D053614:Janus Kinase 2; D019061:src-Family Kinases