Kristen A Marcellus1,2, Tara E Crawford Parks1,2, Shekoufeh Almasi1,2, Bernard J Jasmin3,4. 1. Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H8M5, Canada. 2. The Eric J. Poulin Centre for Neuromuscular Diseases, Ottawa, Ontario, Canada. 3. Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H8M5, Canada. jasmin@uottawa.ca. 4. The Eric J. Poulin Centre for Neuromuscular Diseases, Ottawa, Ontario, Canada. jasmin@uottawa.ca.
Abstract
BACKGROUND: Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer. METHODS: Using a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated. RESULTS: We show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase. CONCLUSIONS: Collectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.
BACKGROUND:Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer. METHODS: Using a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated. RESULTS: We show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase. CONCLUSIONS: Collectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.
Authors: Adrie van Bokhoven; Marileila Varella-Garcia; Christopher Korch; Widya U Johannes; E Erin Smith; Heidi L Miller; Steven K Nordeen; Gary J Miller; M Scott Lucia Journal: Prostate Date: 2003-11-01 Impact factor: 4.104
Authors: Walter Gregory Roberts; Ethan Ung; Pamela Whalen; Beth Cooper; Catherine Hulford; Christofer Autry; Daniel Richter; Earling Emerson; Jing Lin; John Kath; Kevin Coleman; Lili Yao; Luis Martinez-Alsina; Marianne Lorenzen; Martin Berliner; Michael Luzzio; Nandini Patel; Erika Schmitt; Susan LaGreca; Jitesh Jani; Matt Wessel; Eric Marr; Matt Griffor; Felix Vajdos Journal: Cancer Res Date: 2008-03-15 Impact factor: 12.701
Authors: Ker Yu; Celine Shi; Lourdes Toral-Barza; Judy Lucas; Boris Shor; Jae Eun Kim; Wei-Guo Zhang; Robert Mahoney; Christine Gaydos; Luanna Tardio; Sung Kyoo Kim; Roger Conant; Kevin Curran; Joshua Kaplan; Jeroen Verheijen; Semiramis Ayral-Kaloustian; Tarek S Mansour; Robert T Abraham; Arie Zask; James J Gibbons Journal: Cancer Res Date: 2010-01-12 Impact factor: 12.701