Building on the foundation of daring hypotheses: using the MKK4 metastasis suppressor to develop models of dormancy and metastatic colonization.

Abstract

The identification of a novel metastasis suppressor function for the MAP Kinase Kinase 4 protein established a role for the stress-activated kinases in regulating the growth of disseminated cancer cells. In this review, we describe MKK4's biological mechanism of action and how this information is being used to guide the development of new models to study cancer cell dormancy and metastatic colonization. Specifically, we describe the novel application of microvolume structures, which can be modified to represent characteristics similar to those that cancer cells experience at metastatic sites. Although MKK4 is currently one of many known metastasis suppressors, this field of research started with a single daring hypothesis, which revolutionized our understanding of metastasis, and opened up new areas of exploration for basic research. The combination of our increasing knowledge of metastasis suppressors and such novel technologies provide hope for possible clinical interventions to prevent suffering from the burden of metastatic disease.

• Authors: Matthew T Knopeke, Eric T Ritschdorff, Robert Clark, Donald J Vander Griend, Shaheena Khan, Megan Thobe, Jason B Shear, Carrie W Rinker-Schaeffer
• Journal: FEBS letters (FEBS Lett) Vol. 585 Issue 20 Pg. 3159-65 (Oct 20 2011) ISSN: 1873-3468 [Electronic] England
• PMID: 21925502 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Neoplasm Proteins
• MAP Kinase Kinase 4
• MAP2K4 protein, human

Topics

• Antineoplastic Agents (chemistry, therapeutic use)
• Drug Design
• MAP Kinase Kinase 4 (metabolism)
• Models, Biological
• Neoplasm Proteins (genetics, metabolism)
• Neoplastic Cells, Circulating (drug effects, metabolism, pathology)