Erik Sahai

..A branch of the RAS family--the RHO proteins--is also involved in cancer, but what is the role of these proteins and would they make good therapeutic targets?..

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..Strikingly, actomyosin contractility itself positively modulates activity of the transcription factor STAT3 downstream of JAK1, demonstrating positive feedback within the signaling network...

..Combined blockade of extracellular proteases and ROCK negates the ability of tumour cells to switch between modes of motility and synergises to prevent tumour cell invasion...

..We do not observe this pathway in NRAS mutant melanoma or BRAF mutant colorectal cells. Thus, we show that in melanoma cells oncogenic BRAF induces invasion through downregulation of PDE5A...

..These data show reversible phenotype switching during melanoma metastasis...

..We demonstrate tight interplay between Rho and Rac in determining different modes of tumor cell movement, revealing how tumor cells switch between different modes of movement...

..The ability of Dia1 to regulate the actin network is crucial for the localization of adherens junction components to the cell periphery...

..These results support a "tumor microenvironment invasion model" and provide new target opportunities for cancer therapy...

..Instead, carcinoma cells use Cdc42 and MRCK (myotonic dystrophy kinase-related CDC42-binding protein kinases) mediated regulation of MLC to follow the tracks generated by fibroblasts...

..However, the use of genetically encoded fluorescent proteins to distinguish different cell types in living animals has not been described at single cell resolution using multiphoton microscopy...

..ZBP1 reexpression also inhibited metastasis from tumors. These experiments support the involvement in metastasis of the pathways identified in invasive cells, which are regulated by ZBP1...

..These results suggest that ROCK inhibitors would be useful antimetastatic and antiangiogenic chemotherapeutic agents in tumors associated with elevated RhoA, RhoC, ROCK I, or ROCK II expression...

..This work has challenged our views about what causes cancer cells to become motile in the first place, and has demonstrated that cancer cells can move in many different ways...

..In the absence of PDK1, negative regulation by RhoE predominates, causing reduced acto-myosin contractility and motility. This work uncovers a novel non-catalytic role for PDK1 in regulating cortical acto-myosin and cell motility...

..This Review will describe recent advances in our understanding of the different steps of metastasis gained from cellular resolution imaging, and how these techniques can be used in preclinical drug evaluation...

..This review will summarise our current understanding of melanoma invasion and focus on the new model systems that can be used to study melanoma...

..Our results suggest that Smurf1 is a pivotal regulator of tumor cell movement through its regulation of RhoA signaling...

..Imaging of live tumors shows that MLC is organized in a similar ROCK-dependent fashion in vivo and that inhibition of ROCK but not matrix-metalloproteases reduces cancer cell motility in vivo...

..Disruption of this loop by blockade of either EGF receptor or CSF-1 receptor signaling is sufficient to inhibit both macrophage and tumor cell migration and invasion...

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