Tumor focal adhesions

Tamura, M., Gu, J., Matsumoto, K., Aota, S., Parsons, R., and Yamada, K. M. (1998). Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Sdtmce 280, 1614-1617. 

MDM, murine double minute protein with human homolog, neutralizes p53 protein marking it for ubiquitylation (Figure 64). Click for MDM/p53 protein complex rheostat by Eischen CM Lozano G. In FAK (focal adhesion kinase) protein complex, p53 protein is inactive. Click for R2 (Roslin) dismpting FAK/p53 protein complex and liberating p53 protein for action (to block tumor growth) by Golubovskaya VM Ho B Conroy J et al. 

Figure 3. Focal adhesions in (A,B) embryonic fibroblasts and (C,D) tumor cells removed from MMTY-PyMT mice. Cells were plated on fibronectin in serum-free medium. Fibroblasts were stained with rhodamine-phalloidin, FITC conjugated anti-paxillin antibodies, and Hoechst 33258 stain. Tumor cells were stained with rhodamine-phalloidin and FITC conjugated anti-vinculin antibodies. Fluorescence images of the cells were obtained using a decovolution microscope. Paxillin and vinculin (green) are localized to ends of microfilaments (red) in focal adhesions. Mgat5 (A) fibroblasts and (C) tumor cell show focal adhesions but these structures are absent in MgatS (B) fibroblasts and (D) tumor cells. (E), T cell receptor dependent stimulation measured by H-thymi-dine incorporation in response to anti-CD3 antibodies at 48h (F) Model of responses to variable substratum adhesions for Mgat5 and Mgat5 cells.

Mgat5 l breast tumor cells removed from the mice and placed in tissue culture showed impaired focal adhesion formation in low serum conditions (Figure 3). By activating c-Sre/FAK, Shc/RAS and PI3K, the PyMT protein contributes to the reorganization of cytoskeletal structures and turnover of focal-adhesion contacts... 

Weyant MJ, Carothers AM, Dannenberg AJ, Bertagnolli MM. (+)-Catechin inhibits intestinal tumor formation and suppresses focal adhesion kinase activation in the min/+ mouse. Cancer Res 2001 61 118-25. 

In experimentally induced brain focal ischaemia, the upregulation of ICAM-1 and the induction of E- and P-selectm1719 is believed to result from the activity of inflammatory cytokines such as tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6), which are produced by the ischaemic brain20-21 or by the reoxygenation of microvascular endothelial cells.22 There is a direct association between increased expression of ICAM-1 andE-selectin,19-23 the appearance of inflammatory cytokines,20 and the degree of polymorphonuclear (PMN) cell infiltration into ischaemic tissue. Moreover, cultured murine brain microvascular endothelial cells stimulated with IL-1 () or TNF-a express E-selectin and ICAM-1 and support neutrophil adhesion.24... 

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