title: 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.affiliation: The Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637, United States.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Knopeke
authors.forename: Eric T
authors.initials: ET
authors.lastname: Ritschdorff
authors.forename: Robert
authors.initials: R
authors.lastname: Clark
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Vander Griend
authors.forename: Shaheena
authors.initials: S
authors.lastname: Khan
authors.forename: Megan
authors.initials: M
authors.lastname: Thobe
authors.forename: Jason B
authors.initials: JB
authors.lastname: Shear
authors.forename: Carrie W
authors.initials: CW
authors.lastname: Rinker-Schaeffer
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D015195:Drug Design; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human