Experimental validation of the gene expression profiling results indicates that GIPC1 silencing promotes G2 cell-cycle arrest, apoptosis, and alternations in cell adhesion and motility in MDAMB231 human breast cancer cells. GIPC1 depletion correlates with increased caspase 3/7 activity, DNA fragmentation, upregulation of GADD45 family members, and loss of Cdc25b expression. Moreover, GIPC1 silencing correlates with marked reductions in cell viability and evaluations in caspase 3/7 activities in MCF-7 and SKBR-3 human breast cancer and SW480 and SW620 human colorectal cancer cells. By using RNAi to deplete GIPC1 mRNA in MDA-MB-231 cells we were able to identify a wide range of genes whose expression was altered. We compared this GIPC1 signature to publicly available breast and ovarian cancer gene expression datasets for which well-annotated phenotype and outcome data were available. We found Silmitasertib PKC inhibitor strong correlation between the GIPC1 signature and a number of important patient clinical variables. In breast cancer, we used Global Test methodology and found recurrence-free survival was significantly associated with the GIPC1 signature only within specific molecular subtypes of the disease: patients with luminal B ER+ tumors, ERBB2+/ER+ disease, and perhaps basal-like or triple-negative cancers. Within luminal A ER+ cases and patients with ERBB2+/ERcancers, the GIPC1 signature was not predictive of recurrencefree survival. Therefore, the GIPC1 signature may be capable of distinguishing patient outcome within groups of high-grade breast cancers, particularly those that are ER+, and not simply distinguishing tumor grade or ER status. In the ovarian cancer dataset, the GIPC1 signature is statistically correlated with all clinical variables assessed: overall survival and tumor grade, type, and stage. One common feature of the correlations we found between the GIPC1 signature and clinical parameters in breast and ovarian cancer was an association with high-grade tumors that are characterized by excessive DNA damage and poor patient prognosis. The available expression data indicate that GIPC1 is highly expressed in every human cancer and our results suggest GIPC1 is a necessary component for human cancer growth promoted by upstream growth factors and their receptors. Because GIPC1 signal transduction is activated by a wide range of cell-surface PF-04217903 side effects receptors and because it is also known to be essential for branching morphogenesis of arterial blood vessels, targeting GIPC1 mediated pathways is a logical therapeutic strategy for the treatment of human cancers.