Plexin-B1 mutations in prostate cancer.
نویسندگان
چکیده
Semaphorins are a large class of secreted or membrane-associated proteins that act as chemotactic cues for cell movement via their transmembrane receptors, plexins. We hypothesized that the function of the semaphorin signaling pathway in the control of cell migration could be harnessed by cancer cells during invasion and metastasis. We now report 13 somatic missense mutations in the cytoplasmic domain of the Plexin-B1 gene. Mutations were found in 89% (8 of 9) of prostate cancer bone metastases, in 41% (7 of 17) of lymph node metastases, and in 46% (41 of 89) of primary cancers. Forty percent of prostate cancers contained the same mutation. Overexpression of the Plexin-B1 protein was found in the majority of primary tumors. The mutations hinder Rac and R-Ras binding and R-RasGAP activity, resulting in an increase in cell motility, invasion, adhesion, and lamellipodia extension. These results identify a key role for Plexin-B1 and the semaphorin signaling pathway it mediates in prostate cancer.
منابع مشابه
Effect of prostate cancer-related plexin-B1 mutations on cell signalling and function
DECLARATION I declare that this thesis represents my own work. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Hodgkin Postgraduate Award for funding me during my PhD study. I would also like to give my sincere thanks to my supervisor Professor John W. Masters for funding and supervising me throughout my research work. I am extremely ...
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عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 104 48 شماره
صفحات -
تاریخ انتشار 2007