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首页> 美国政府科技报告 >Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness
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Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

机译：机械敏感性Ca2 +通道作为前列腺肿瘤细胞迁移和侵袭的中心规律

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A major challenge for treating prostate cancer (PC) is to discover new therapies that will prevent the spread of PC cells from the prostate to distal sites. Our research focuses on the stretch-activated mechanosensitive Ca2+ permeant channel (MscCa) as a central regulator of prostate tumor cell migration. Our experiments are designed to address the two most basic issues of the disease: the mechanism(s) that trigger progression of PC to malignancy and the urgent need for new therapeutic targets to block or reverse this progression. Our original experiments funded by DOD were aimed to test whether MscCa is expressed in human prostate tumor cells and whether MscCa activity is required for prostate tumor cell migration. We confirmed both results. In the course of these experiments we also discovered that the predominate gating mode of the MscCa differs between noninvasive and invasive PC cells, may be the most powerful determinate of the (Ca2+)i dynamics required to coordinate cell locomotion. The aims of the current award were three-fold. First, determine the mechanisms underlying MscCa gating. Second, determine the cancer-related processes that switch MscCa gating, and third determine whether anti-MscCa conditions that suppress PC migration in vitro also block PC cell invasion in vivo. Insights into these aspects would provide added motivation for developing more selective therapies that target MscCa and its regulatory mechanisms. The basic results supporting our hypothesis have been published (Maroto, R. & Hamill, O.P. MscCa regulation of tumor cell migration and metastasis. Current Topics in Membranes.59, 485-509, 2007). Also included in the Appendix are other manuscripts and abstracts (Hamill & Maroto 2007; 2008; Gotlieb et al., 2008; Maroto & Hamill, 2011; and Maroto, Kurosky and Hamill, 2011) that include specific results described in body of the text.

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