ARTHUR MERCURIO

..These findings imply that VEGF and VEGF receptor-based therapeutics, in addition to targeting angiogenesis, may also target tumor cells directly...

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..Thus, the EMT appears to be an integral component of colorectal cancer progression and its analysis can yield novel targets for prognosis and therapy...

..Importantly, this mechanism is manifested in high Gleason grade cancers, which exhibit significantly more HIF-1alpha and VEGF expression, and Snail1 nuclear localization compared to low Gleason grade cancers...

..Our data indicate that complex epigenetic modifications contribute to the regulation of the beta 4 integrin and E-cadherin...

..Collectively, our data indicate that Irs-2, but not Irs-1, promotes invasion by sustaining the aerobic glycolysis of mouse mammary tumor cells and that it does so by regulating the mTor-dependent surface expression of Glut1...

..These data provide a mechanism for the regulation of Tiam1-mediated Rac activation in breast cancer cells and need to be considered in the context of other reported functions for miR-10b...

..These data also question the putative role of the beta4 intracellular domain as an "adaptor" for growth factor receptor signaling...

..Data on its expression and relevance to human carcinomas, however, are relatively scant. The aim of this study was to assess its expression and prognostic significance in human breast carcinomas...

..Therefore, IAPs are direct metastasis genes, and their antagonists could provide antimetastatic therapies in patients with cancer...

..Studies aimed at assessing NRP function and targeted therapy in cancer and angiogenesis should consider the impact of metabolic stress...

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..These data provide a compelling argument for the importance of both p120ctn and the EMT itself in the progression of colorectal carcinoma...

..Taken together, these data implicate the alpha6beta4 integrin in tumor formation by regulating tumor cell survival in a VEGF-dependent manner...

..This mechanism links active H-Ras, transcriptionally active E2F, and the alpha6beta4 integrin in a common pathway that culminates in enhanced alpha6beta4-dependent invasion...

..These findings provide one mechanism to account for the activation of PI3K by alpha(6)beta(4) and they also provide insight into the regulation of ErbB-3 in carcinoma cells...

..This increase is dependent on Rab11 and stable microtubules. In summary, we identify vesicle trafficking as a novel target of hypoxic stimulation that is important for tumor invasion...

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..These results establish a novel role for the stroma in influencing EMT in colon carcinoma, and they identify a selective advantage to the stromal presence of infiltrating leukocytes in regulating malignant tumor progression...

..These data argue that the invasive function of Met can be independent of alpha(6)beta(4) and that alpha(6)beta(4) has a generic influence on the invasion of carcinoma cells that is not specific to Met...

..VEGF produced by breast carcinoma cells in response to alpha6 integrin regulation can function in an autocrine manner to promote survival signaling...

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..These studies establish that the regulated expression of a specific chemokine and its receptor are linked to the EMT and they provide a biochemical framework for understanding the mechanisms by which the EMT promotes migration...

..Our findings indicate that a VEGF autocrine pathway induces chemokine receptor expression in breast carcinoma cells, thus promoting their directed migration toward specific chemokines...

..These findings reveal that integrin-mediated activation of PI-3K-Akt is amplified by integrin-stimulated VEGF expression and they provide a mechanism that substantiates the reported role of alpha 6 beta 4 in carcinoma progression...

..These findings define the alphavbeta6 integrin as an important risk factor for early-stage disease and a novel therapeutic candidate for colorectal cancer...

..Our findings lead to the surprising conclusion that opposing autocrine loops involving NP1 regulate the chemotaxis of breast carcinoma cells. Moreover, our data indicate a novel autocrine function for VEGF in chemotaxis...

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..A role for Flt-1 in cell survival is unprecedented and has significant implications for Flt-1 function in tumor progression, as well as in other biological processes, including angiogenesis and development...

..Furthermore, these data suggest that the utilization of siRNA oligonucleotides to reduce the expression of the alpha6beta4 integrin may be a useful approach to prevent carcinoma cell progression...

..Our model allows the assessment of epigenetic changes that occur during human carcinogenesis. In addition, these studies provide insight into the clinical failure of tyrosine kinase inhibitors as monotherapy for advanced malignancy...

..Unexpectedly, this analysis also revealed a compensatory relationship between RhoA and RhoC at the level of both their expression and activation, and a reciprocal relationship between RhoA and Rac1 activation...

..Together, these results show that the ability of ADAM12 to influence apoptosis may contribute to tumor progression...

..These findings indicate that epithelial cells must sustain activation of a specific kinase to impede a mesenchymal transition...

..Overall, the reported findings indicate that alpha 6 beta 4 integrin promotes growth arrest and differentiation by modulating Abl kinases and p73 protein pathway(s)...

..For this reason, a rigorous understanding of the mechanisms used in this signaling and its relevance to breast cancer is essential. ..

..Aim 4 will undertake a rigorous analysis of N-cadherin regulation by p120ctn. ..

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..The goals of this proposal are to understand how the proteins encoded by these genes contribute to breast cancer and how their functions are inter-related. ..

..For this reason, a rigorous understanding of the mechanisms used in this signaling and its relevance to breast cancer is essential. ..

..The goals of this proposal are to understand how the proteins encoded by these genes contribute to breast cancer and how their functions are inter-related. ..

..Collectively, the results obtained from this study will establish a novel mechanism that regulates the survival of metastatic breast carcinoma cells. ..

..The goals of this proposal are to understand how the proteins encoded by these genes contribute to breast cancer and how their functions are inter-related. ..