Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells Journal Article
| Authors: | Miller, S. L.; Antico, G.; Raghunath, P. N.; Tomaszewski, J. E.; Clevenger, C. V. |
| Article Title: | Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells |
| Abstract: | Prolactin (PRL) stimulates the cytoskeletal re-organization and motility of breast cancer cells. During PRL receptor signaling, Vav2 becomes phosphorylated and activated, an event regulated by the serine/threonine kinase Nek3. Given the regulatory role of Vav2, the function of Nek3 in PRL-mediated motility and invasion was examined. Overexpression of Nek3 in Chinese hamster ovary transfectants potentiated cytoskeletal re-organization in response to PRL. In contrast, downregulation of Nek3 expression by small-interfering RNA (siRNA) attenuated PRL-mediated cytoskeletal reorganization, activation of GTPase Rac1, cell migration and invasion of T47D cells. In addition, PRL stimulation induced an interaction between Nek3 and paxillin and significantly increased paxillin serine phosphorylation, whereas Nek3 siRNA-transfected cells showed a marked reduction in paxillin phosphorylation. Analysis of breast tissue microarrays also demonstrated a significant up-regulation of Nek3 expression in malignant versus normal specimens. These data suggest that Nek3 contributes to PRL-mediated breast cancer motility through mechanisms involving Rac1 activation and paxillin phosphorylation. © 2007 Nature Publishing Group All rights reserved. |
| Keywords: | controlled study; protein expression; protein phosphorylation; unclassified drug; nonhuman; protein function; animal cell; animals; gene overexpression; breast cancer; serine; small interfering rna; rna, small interfering; cancer cell culture; cell line, tumor; transfection; protein serine threonine kinase; breast neoplasms; phosphorylation; cancer invasion; protein-serine-threonine kinases; cell migration; cell movement; down regulation; neoplasm invasiveness; upregulation; molecular interaction; tissue microarray; cytoskeleton; cell motility; invasion; prolactin; cho cell; cho cells; cricetinae; cricetulus; cricetulus griseus; rac; cell ultrastructure; rac1 protein; rac1 gtp-binding protein; paxillin; vav2; serine threonine protein kinase 3; proto-oncogene proteins c-vav |
| Journal Title: | Oncogene |
| Volume: | 26 |
| Issue: | 32 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2007-07-12 |
| Start Page: | 4668 |
| End Page: | 4678 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1210264 |
| PUBMED: | 17297458 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 14" - "Export Date: 17 November 2011" - "CODEN: ONCNE" - "Source: Scopus" |
