NEK5 activity regulates the mesenchymal and migratory phenotype in breast cancer cells

Purpose Breast cancer remains a prominent global disease affecting women worldwide despite the emergence of novel therapeutic regimens. Metastasis is responsible for most cancer-related deaths, and acquisition of a mesenchymal and migratory cancer cell phenotypes contributes to this devastating disease. The utilization of kinase targets in drug discovery have revolutionized the field of cancer research but despite impressive advancements in kinase-targeting drugs, a large portion of the human kinome remains understudied in cancer. NEK5, a member of the Never-in-mitosis kinase family, is an example of such an understudied kinase. Here, we characterized the function of NEK5 in breast cancer. Methods Stably overexpressing NEK5 cell lines (MCF7) and shRNA knockdown cell lines (MDA-MB-231, TU-BcX-4IC) were utilized. Cell morphology changes were evaluated using immunofluorescence and quantification of cytoskeletal components. Cell proliferation was assessed by Ki-67 staining and transwell migration assays tested cell migration capabilities. In vivo experiments with murine models were necessary to demonstrate NEK5 function in breast cancer tumor growth and metastasis. Results NEK5 activation altered breast cancer cell morphology and promoted cell migration independent of effects on cell proliferation. NEK5 overexpression or knockdown does not alter tumor growth kinetics but promotes or suppresses metastatic potential in a cell type-specific manner, respectively. Conclusion While NEK5 activity modulated cytoskeletal changes and cell motility, NEK5 activity affected cell seeding capabilities but not metastatic colonization or proliferation in vivo. Here we characterized NEK5 function in breast cancer systems and we implicate NEK5 in regulating specific steps of metastatic progression

Communication with old people

Predicted drug-target-disease associations using OMIM. For each human protein target crystal structure, the top 40-ranked drugs were associated with a disease through their predicted target. (XLSX 464 kb

Additional file 5: Table S5. of DrugGenEx-Net: a novel computational platform for systems pharmacology and gene expression-based drug repurposing

Consensus drug rank list for Inflammatory Bowel Disease. (XLS 51 kb

Additional file 2: Table S2. of DrugGenEx-Net: a novel computational platform for systems pharmacology and gene expression-based drug repurposing

Validations of predicted drug-disease associations from the literature. (XLS 38 kb

The psychological effects of empowerment strategies on consumers' product demand

Companies have recently begun to use the Internet in order to integrate their customers more actively into various phases of the new product development (NPD) process. One such strategy involves empowering customers to cooperate in selecting the product concepts to be marketed by the firm. In such scenarios, it is no longer the company but its customers who decide democratically which products should be produced. This article discusses the first set of empirical studies which highlight the important psychological consequences of this power shift. The results indicate that customers who are empowered to select the products to be marketed will show stronger demand for the underlying products even though they are of identical quality in objective terms (and their subjective product evaluations are similar). This seemingly irrational finding can be observed because consumers develop a stronger feeling of psychological ownership of the products selected. The studies also identify two boundary conditions for this "empowerment – product demand" effect: It diminishes if the outcome of the joint decisionmaking process does not reflect consumers' preferences and if consumers do not feel that they have the relevant competence to make sound decisions