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Stat3 promotes metastatic progression of prostate cancer

Abdulghani, J. and Gu, L. and Dagvadorj, A. and Lutz, J. and Leiby, B. and Bonuccelli, G. and Lisanti, M. P. and Zellweger, T. and Alanen, K. and Mirtti, T. and Visakorpi, T. and Bubendorf, L. and Nevalainen, M. T.. (2008) Stat3 promotes metastatic progression of prostate cancer. American Journal of Pathology, Vol. 172, no. 6. pp. 1717-1728.

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Official URL: http://edoc.unibas.ch/dok/A6003509

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Abstract

There are currently no effective therapies for metastatic prostate cancer because the molecular mechanisms that underlie the metastatic spread of primary prostate cancer are unclear. Transcription factor Stat3 is constitutively active in malignant prostate epithelium, and its activation is associated with high histological grade and advanced cancer stage. In this work, we hypothesized that Stat3 stimulates metastatic progression of prostate cancer. We show that Stat3 is active in 77% of lymph node and 67% of bone metastases of clinical human prostate cancers. Importantly, adenoviral gene delivery of wild-type Stat3 (AdWTStat3) to DU145 human prostate cancer cells increased the number of lung metastases by 33-fold in an experimental metastasis assay compared with controls. Using various methods to inhibit Stat3, we demonstrated that Stat3 promotes human prostate cancer cell migration. Stat3 induced the formation of lamellipodia in both DU145 and PC-3 cells, further supporting the concept that Stat3 promotes a migratory phenotype of human prostate cancer cells. Moreover, Stat3 caused the rearrangement of cytoplasmic actin stress fibers and microtubules in both DU145 and PC-3 cells. Finally, inhibition of the Jak2 tyrosine kinase decreased both activation of Stat3 and prostate cancer cell motility. Collectively, these data indicate that transcription factor Stat3 is involved in metastatic behavior of human prostate cancer cells and may provide a therapeutic target to prevent metastatic spread of primary prostate cancer.
Faculties and Departments:03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Stammzellpathologie (Bubendorf)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Stammzellpathologie (Bubendorf)
UniBasel Contributors:Bubendorf, Lukas and Zellweger, Tobias
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Investigative Pathology
ISSN:0002-9440
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:16

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