Knockdown of cathepsin B and uPAR inhibits CD151 and α3β1 integrin-mediated cell adhesion and invasion in glioma.
作者： Rama Rao Malla , Sreelatha Gopinath , Kiranmai Alapati , Bharathi Gorantla , Christopher S. Gondi
DOI: 10.1002/MC.21915
关键词: Cell adhesion 、 Cathepsin B 、 Cancer research 、 Biology 、 Urokinase receptor 、 Integrin alpha3beta1 、 Cell adhesion molecule 、 Vinculin 、 Integrin 、 Paxillin
摘要: Glioma is a highly complex brain tumor characterized by the dysregulation of proteins and genes that leads to metastasis. Cathepsin B uPAR are overexpressed in gliomas they postulated play central roles glioma In this study, efficient downregulation cathepsin siRNA treatments significantly reduced cell adhesion laminin as compared vitronectin, fibronectin, or collagen I U251 4910 lines. Brain tissue array analysis showed high expression CD151 clinical samples when with normal tissue. treatment led laminin-binding integrins α3 β1. Co-immunoprecipitation experiments revealed decreased interaction B, α3β1 integrin. Studies on downstream signaling cascade uPAR/CD151/α3β1 integrin have shown phosphorylation FAK, SRC, paxillin, adaptor cytoskeletal talin vinculin were knockdown uPAR, CD151. Treatment bicistronic construct interactions between well lowering integrin, talin, levels pre-established tumors nude mice. conclusion, our results show alone combination inhibit downregulating its associated molecules vitro vivo. Taken together, present study targeting uPAR-cathepsin system has possible therapeutic potential.
sci-hub.se 参考文章(44)
Julio A. Aguirre-Ghiso, Liliana Ossowski, Yeriel Estrada, David Liu, ERKMAPK Activity as a Determinant of Tumor Growth and Dormancy; Regulation by p38SAPK Cancer Research. ,vol. 63, pp. 1684- 1695 ,(2003)
H K Kleinman, A Albini, G R Martin, S A Aaronson, Y Iwamoto, R N McEwan, J M Kozlowski, A Rapid in Vitro Assay for Quantitating the Invasive Potential of Tumor Cells Cancer Research. ,vol. 47, pp. 3239- 3245 ,(1987)
Ramarao Malla, Sreelatha Gopinath, Kiranmai Alapati, Christopher S. Gondi, Meena Gujrati, Dzung H. Dinh, Sanjeeva Mohanam, Jasti S. Rao, Downregulation of uPAR and Cathepsin B Induces Apoptosis via Regulation of Bcl-2 and Bax and Inhibition of the PI3K/Akt Pathway in Gliomas PLOS ONE. ,vol. 5, ,(2010) , 10.1371/JOURNAL.PONE.0013731
Philippe R. J. Bois, Brendan P. O'Hara, Daniel Nietlispach, John Kirkpatrick, Tina Izard, The Vinculin Binding Sites of Talin and α-Actinin Are Sufficient to Activate Vinculin Journal of Biological Chemistry. ,vol. 281, pp. 7228- 7236 ,(2006) , 10.1074/JBC.M510397200
Roland H. Goldbrunner, Jerald J. Bernstein, Jörg-Christian Tonn, ECM‐mediated glioma cell invasion Microscopy Research and Technique. ,vol. 43, pp. 250- 257 ,(1998) , 10.1002/(SICI)1097-0029(19981101)43:3<250::AID-JEMT7>3.0.CO;2-C
Jasti S. Rao, Molecular mechanisms of glioma invasiveness: the role of proteases. Nature Reviews Cancer. ,vol. 3, pp. 489- 501 ,(2003) , 10.1038/NRC1121
Arun Kumar Nalla, Swapna Asuthkar, Praveen Bhoopathi, Meena Gujrati, Dzung H. Dinh, Jasti S. Rao, Suppression of uPAR Retards Radiation-Induced Invasion and Migration Mediated by Integrin β1/FAK Signaling in Medulloblastoma PLoS ONE. ,vol. 5, pp. e13006- ,(2010) , 10.1371/JOURNAL.PONE.0013006
Masashi Kohno, Hitoshi Hasegawa, Masayuki Miyake, Tadashi Yamamoto, Shigeru Fujita, CD151 enhances cell motility and metastasis of cancer cells in the presence of focal adhesion kinase. International Journal of Cancer. ,vol. 97, pp. 336- 343 ,(2002) , 10.1002/IJC.1605
Harvey W. Smith, Chris J. Marshall, Regulation of cell signalling by uPAR Nature Reviews Molecular Cell Biology. ,vol. 11, pp. 23- 36 ,(2010) , 10.1038/NRM2821
A K Nalla, B Gorantla, C S Gondi, S S Lakka, J S Rao, Targeting MMP-9, uPAR, and cathepsin B inhibits invasion, migration and activates apoptosis in prostate cancer cells. Cancer Gene Therapy. ,vol. 17, pp. 599- 613 ,(2010) , 10.1038/CGT.2010.16