Modulation of Cell Migration and Invasiveness by Tumor Suppressor TSC2 in Lymphangioleiomyomatosis
作者： Elena A. Goncharova , Dmitriy A. Goncharov , Poay N. Lim , Daniel Noonan , Vera P. Krymskaya
关键词: Mesenchymal stem cell 、 Gene knockdown 、 Biology 、 Focal adhesion 、 Cell migration 、 TSC1 、 Cancer research 、 TSC2 、 RHOA 、 Lymphangioleiomyomatosis
摘要: The loss of TSC2 function is associated with the pathobiology lymphangioleiomyomatosis (LAM), which characterized by abnormal proliferation, migration, and differentiation smooth muscle–like cells within lungs. Although etiology LAM remains unknown, clinical genetic evidence provides support for neoplastic nature LAM. goal this study was to determine role tumor suppressor in potential cells. We show that primary cultures human exhibit increased migratory activity invasiveness, abolished re-expression. found also inhibits cell migration through its N-terminus, independent GTPase-activating protein activity. stress fiber focal adhesion formation, attenuated small GTPase RhoA activated compared normal mesenchymal Pharmacologic inhibition Rho abrogates migration; re-expression or TSC1 knockdown specific siRNA. These data demonstrate controls N-terminus associating regulating activity, suggesting may play a critical modulating contributes
sci-hub.se 参考文章(47)
Mervyn J Merrilees, Elyshia J Hankin, Judith L Black, Brent Beaumont, Matrix proteoglycans and remodelling of interstitial lung tissue in lymphangioleiomyomatosis. The Journal of Pathology. ,vol. 203, pp. 653- 660 ,(2004) , 10.1002/PATH.1577
Magdalena Karbowniczek, Aristotelis Astrinidis, Binaifer R. Balsara, Joseph R. Testa, James H. Lium, Thomas V. Colby, Francis X. McCormack, Elizabeth Petri Henske, Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism. American Journal of Respiratory and Critical Care Medicine. ,vol. 167, pp. 976- 982 ,(2003) , 10.1164/RCCM.200208-969OC
Li Ma, Zhenbang Chen, Hediye Erdjument-Bromage, Paul Tempst, Pier Paolo Pandolfi, Phosphorylation and Functional Inactivation of TSC2 by Erk Cell. ,vol. 121, pp. 179- 193 ,(2005) , 10.1016/J.CELL.2005.02.031
Dos D. Sarbassov, Siraj M Ali, Do-Hyung Kim, David A Guertin, Robert R Latek, Hediye Erdjument-Bromage, Paul Tempst, David M Sabatini, Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton Current Biology. ,vol. 14, pp. 1296- 1302 ,(2004) , 10.1016/J.CUB.2004.06.054
G. Finlay, The LAM cell: what is it, where does it come from, and why does it grow? American Journal of Physiology-lung Cellular and Molecular Physiology. ,vol. 286, pp. 690- 693 ,(2004) , 10.1152/AJPLUNG.00311.2003
P. B. Crino, E. P. Henske, New developments in the neurobiology of the tuberous sclerosis complex Neurology. ,vol. 53, pp. 1384- 1384 ,(1999) , 10.1212/WNL.53.7.1384
Erik Sahai, Christopher J. Marshall, Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nature Cell Biology. ,vol. 5, pp. 711- 719 ,(2003) , 10.1038/NCB1019
Jeremy P. Cheadle, Mary Pat Reeve, Julian R. Sampson, David J. Kwiatkowski, Molecular genetic advances in tuberous sclerosis Human Genetics. ,vol. 107, pp. 97- 114 ,(2000) , 10.1007/S004390000348
Aristotelis Astrinidis, Timothy P Cash, Deborah S Hunter, Cheryl L Walker, Jonathan Chernoff, Elizabeth P Henske, Tuberin, the tuberous sclerosis complex 2 tumor suppressor gene product, regulates Rho activation, cell adhesion and migration. Oncogene. ,vol. 21, pp. 8470- 8476 ,(2002) , 10.1038/SJ.ONC.1205962
J. Mark Madison, Migration of airway smooth muscle cells. American Journal of Respiratory Cell and Molecular Biology. ,vol. 29, pp. 8- 11 ,(2003) , 10.1165/RCMB.F272