Src kinase inhibitors: an emerging therapeutic treatment option for prostate cancer

Edwards, Joanne

doi:10.1517/13543781003789388

Cited by 34 publications

(27 citation statements)

References 75 publications

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“…In a clinical study of patients with advanced solid tumors, dasatinib therapy alone was reported to be acceptable and well tolerated with some preliminary evidence of efficacy (41). Additionally, phase I and II studies of CRPC patients treated with a combination of dasatinib and docetaxel show a reduction in the size and/or number of existing bone lesions (42,43). Our study shows that dasatinib inhibits invasive carcinoma and EMT induced by expression of constitutively active Src kinase.…”

Section: Discussionmentioning

confidence: 56%

Invasive Prostate Carcinoma Driven by c-Src and Androgen Receptor Synergy

et al. 2011

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Cellular Src (c-Src) integrates a large number of signal transduction pathways regulating cell division, migration, and other aspects of cell physiology. Mutations of Src kinase have not been described in human prostate cancer, but evidence for increased levels of expression accompanying cancer progression has been reported. We analyzed overexpression of c-Src in naïve mouse prostate epithelium and observed no change in tubule formation frequency or histologic structure. However, when enhanced c-Src expression is coupled with enhanced expression of androgen receptor (AR), it results in a strong activation of Src kinase activity accompanied by activation of the MAPK pathway, and enhanced AR activity. Similar to the pathology induced by constitutively active c-Src(Y529F), the tubules progress to frank carcinoma with invasion and display markers of epithelial-to-mesenchymal transition. These combined results suggest that nonmutated Src kinase may play a more important role in the genesis and progression of prostate cancer than previously appreciated and that epigenetic changes that enhance the level of AR may select for enhanced expression of c-Src with accompanying activation and a strong drive to malignant progression. Cancer Res; 71(3); 862-72. Ó2010 AACR.

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Section: Discussionmentioning

confidence: 56%

Invasive Prostate Carcinoma Driven by c-Src and Androgen Receptor Synergy

et al. 2011

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“…Many of these interactions are highly dependent on the kinase function of the SFK. Overexpression and/or elevated activation of SFKs occur frequently in tumor tissues, leading to alterations in cellular growth, shape and function, and making the SFKs attractive targets for anti-cancer treatment in several solid tumors and leukemia (Kim et al, 2009;Edwards, 2010).…”

Section: Introductionmentioning

confidence: 99%

microRNA-125a-3p reduces cells proliferation and migration by targeting Fyn

Ninio-Many

Grossman

Shomron

et al. 2013

Journal of Cell Science

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SummaryFyn, a member of the Src family kinases (SFKs), has a pivotal role in cell adhesion, proliferation, migration and survival, and its overexpression is associated with several types of cancer. MicroRNAs (miRNAs) play a major role in post-transcriptional repression of protein expression. In light of the significant functions of Fyn, together with studies demonstrating miR-125a as a tumor-suppressing miRNA that is downregulated in several cancer cell types and on our bioinformatics studies presented here, we chose to examine the post-transcription regulation of Fyn by miR-125a-3p in the HEK 293T cell line. We show that Fyn expression can be dramatically reduced by elevated levels of miR-125a-3p. Following this reduction, the activity of proteins downstream of Fyn, such as FAK, paxillin and Akt (proteins known to be overexpressed in various tumors), is also reduced. On a broader level, we show that miR-125a-3p causes an arrest of the cell cycle at the G2/M stage and decreases cell viability and migration, probably in a Fyn-directed manner. The results are reinforced by control experiments conducted using Fyn siRNA and anti-miR-125a-3p, as well as by the fact that numerous cancer cell lines show a significant downregulation of Fyn after mir-125a-3p overexpression. Collectively, we conclude that miR-125a-3p has an important role in the regulation of Fyn expression and of its signaling pathway, which implies that it has a therapeutic potential in overexpressed Fyn-related diseases.

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“…7(14%) patients were of pathological fracture. In males, cancers of the prostate and lungs make up 80% of the carcinomas that metastasize to bone [Edwards J et al 2010) The remaining 20% of primary disease sites in patients of both sexes are the kidney, gut, and thyroid as well as sites of unknown origin.…”

Section: Resultsmentioning

confidence: 99%