https://scholars.lib.ntu.edu.tw/handle/123456789/634756
標題: | Nestin depletion induces melanoma matrix metalloproteinases and invasion | 作者: | Lee, Chung-Wei Zhan, Qian Lezcano, Cecilia Frank, Markus H JOHN HUANG Larson, Allison R Lin, Jennifer Y Wan, Marilyn T Lin, Ping-I Ma, Jie Kleffel, Sonja Schatton, Tobias Lian, Christine G Murphy, George F |
公開日期: | 十二月-2014 | 卷: | 94 | 期: | 12 | 來源出版物: | Laboratory investigation; a journal of technical methods and pathology | 摘要: | Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because cytoskeletal changes are known to accompany MMP expression, we sought to examine the potential role of the poorly understood cytoskeletal protein, nestin, in modulating melanoma MMPs. Nestin knockdown (KD) upregulated the expression of specific MMPs and MMP-dependent invasion both through extracellular matrix barriers in vitro and in peritumoral connective tissue of xenografts in vivo. The development of three-dimensional melanospheres that in vitro partially recapitulate noninvasive tumorigenic melanoma growth was inhibited by nestin KD, although ECM invasion by aberrant melanospheres that did form was enhanced. Mechanistically, nestin KD-dependent melanoma invasion was associated with intracellular redistribution of phosphorylated focal adhesion kinase and increased melanoma cell responsiveness to transforming growth factor-beta, both implicated in pathways of melanoma invasion. The results suggest that the heretofore poorly understood intermediate filament, nestin, may serve as a novel mediator of MMPs critical to melanoma virulence. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/634756 | ISSN: | 00236837 | DOI: | 10.1038/labinvest.2014.130 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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