A novel myosin and its role in metastatic prostate cancer
Domaradzki, Tera M.
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The majority of death from prostate cancer is caused by metastasis, the spreading of cancer cells from the primary tumors throughout the body. Yet, there is a distinct lack of understanding of the cellular factors and mechanisms that contribute to the spreading of prostate cancer cells. Recently, a novel myosin IC isoform (isoform A) was discovered that is selectively overexpressed in prostate cancer tumor tissues and in mouse and human prostate cancer cell lines. The goal of this study was to determine the biological and physiological significance of this prostate cancer-related expression pattern of isoform A. I found that isoform A associates with caveolin-1 containing vesicles in the perinuclear region and along lamellipodial protrusions, and I found an association of isoform A with extracellular secreted vesicles. Furthermore, I show that this association between isoform A and secretory vesicles is facilitated by the myosin IC tail region. Expression of a loss-of function isoform A mutant, as well as silencing of isoform A through expression of isoform A-specific shRNA constructs, led to a significant reduction in the invasive abilities of the PC-3 prostate cancer cells suggesting a critical role for isoform A in cancer cell invasion. An analysis of the genomic region upstream of the isoform A transcription start site revealed suggests a possible involvement of the transcription regulator p300 in the prostate cancer-specific expression of isoform A. Taken together, my data demonstrate the identification of a new factor that is critically involved in the development of aggressive prostate cancer that could be a potential new therapeutic target.