https://scholars.lib.ntu.edu.tw/handle/123456789/416780
標題: | The Shp2-induced epithelial disorganization defect is reversed by HDAC6 inhibition independent of Cdc42 | 作者: | Tien, Sui-Chih Lee, Hsiao-Hui Yang, Ya-Chi MIAO-HSIA LIN Chen, Yu-Ju ZEE-FEN CHANG |
公開日期: | 19-一月-2016 | 出版社: | NATURE PUBLISHING GROUP | 卷: | 7 | 期: | 1 | 來源出版物: | Nature communications | 摘要: | Regulation of Shp2, a tyrosine phosphatase, critically influences the development of various diseases. Its role in epithelial lumenogenesis is not clear. Here we show that oncogenic Shp2 dephosphorylates Tuba to decrease Cdc42 activation, leading to the abnormal multi-lumen formation of epithelial cells. HDAC6 suppression reverses oncogenic Shp2-induced multiple apical domains and spindle mis-orientation during division in cysts to acquire normal lumenogenesis. Intriguingly, Cdc42 activity is not restored in this rescued process. We present evidence that simultaneous reduction in myosin II and ERK1/2 activity by HDAC6 inhibition is responsible for the reversion. In HER2-positive breast cancer cells, Shp2 also mediates Cdc42 repression, and HDAC6 inhibition or co-suppression of ERK/myosin II promotes normal epithelial lumen phenotype without increasing Cdc42 activity. Our data suggest a mechanism of epithelial disorganization by Shp2 deregulation, and reveal the cellular context where HDAC6 suppression is capable of establishing normal epithelial lumenogenesis independent of Cdc42. |
URI: | https://api.elsevier.com/content/abstract/scopus_id/84955134291 https://scholars.lib.ntu.edu.tw/handle/123456789/416780 |
ISSN: | 2041-1723 | DOI: | 10.1038/ncomms10420 |
顯示於: | 分子醫學研究所 |
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