FADD bridges the death receptors to the death inducing signaling com plex and activates caspase 8. Active caspase 8 initiates a cascade of caspases which mediate apoptosis. Another example is a large increase in the expression of DIO 1 that translocates to the nucleus and activates apoptosis in cell culture. KIAA1199 knockdown also led to up regulation of A kinase anchor Enzastaurin mw protein 8 that is a potential carrier protein for active caspase 3, carrying it from the cytoplasm into the nuclei in apoptotic cells and is in volved in the process of apoptotic nuclear morphological change. It is noteworthy that we found progesterone recep tor membrane component 1 down regulated upon KIAA1199 knockdown. This protein promotes cell survival in human cancer after chemotherapy.

PGRMC1 was reported to be over expressed in breast tumors and other cancer cell lines. It is known that high expression of BAX is associated with Inhibitors,Modulators,Libraries improved chemotherapy responsiveness whereas PGRMC1 has a negative impact on chemotherapy by promoting the survival of treated cancer cells. This knowledge plus the fact that KIAA1199 knockdown al ters the expression level of these proteins, suggests that KIAA1199 depletion may potentially improve cellular response to chemotherapy. Our wound Inhibitors,Modulators,Libraries healing and transwell cell motility assays showed lower motility in the MDA MB 231 ShB cells. These findings can be explained by the observation of altered levels of proteins involved in cellular shape change, filopodia extension, nuclear migration and adhesion in hibition in the knockdown cells.

We observed the up regulation Inhibitors,Modulators,Libraries of S100A11 protein which Inhibitors,Modulators,Libraries functions in tubulin polymerization, motility, and tumor invasion and down regulation of the transforming acidic coiled coil containing protein 3. The latter plays a role in the microtubule dependent coupling Inhibitors,Modulators,Libraries of the nucleus and the centrosome, and it has been demonstrated to be over expressed in various cancer cell lines. Furthermore, TACC3 depletion has been reported to strongly sensitize cells to chemotherapy, therefore KIAA1199 depletion can also potentially affect the cellular response to chemo therapy via TACC3. Neural Wiskott Aldrich syndrome protein is dramatically down regulated in the KIAA1199 knockdown cells. WASL activates the Arp2 3 complex required for the extension of lamellipodia and filopodia during cell movement.

Another down regulated protein is Neurabin 2 which binds along the sides of F actin Compound C and plays a role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. PPP1R9B therefore might be involved in cell shape change and migration. A member of the tenas cin protein family, the glycoprotein tenascin X is also dramatically down regulated in the KIAA1199 knock down cells. As opposed to fibronectin which is adhesive, the tenascins have anti adhesive effects. TNXB mediates interactions between cells and the extracellular matrix and may support the growth of epithelial tumors.