title: An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma.
abstract: The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated. Here we demonstrate that MMB is required for tumor formation in a mouse model of lung cancer driven by oncogenic K-RAS. We also identify a requirement for the mitotic kinesin KIF23, a key target gene of MMB, in tumorigenesis. RNA interference-mediated depletion of KIF23 inhibited lung tumor formation in vivo and induced apoptosis in lung cancer cell lines. Our results suggest that inhibition of KIF23 could be a strategy for treatment of lung cancer.
authors.affiliation: Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Iltzsche
authors.affiliation: Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Simon
authors.affiliation: Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Stopp
authors.affiliation: Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Pattschull
authors.affiliation: Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Francke
authors.affiliation: Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Wolter
authors.affiliation: Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hauser
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, and the CRUK Beatson Institute, Glasgow, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Murphy
authors.affiliation: Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: P
authors.initials: P
authors.lastname: Garcia
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany.|Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: Department of Physiological Chemistry, Biocenter, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany.|Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Gaubatz
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: D046912:Multiprotein Complexes; D020598:Proto-Oncogene Proteins c-myb; C541430:MKLP1 protein, mouse; D016547:Kinesins