title: Heat shock transcription factor (HSF1) plays a critical role in cell migration via maintaining MAP kinase signaling.
abstract: Upon cancer progression in mouse models of prostate cancer, the heat shock transcription factor Hsf1 becomes strongly upregulated, especially in metastases. We hypothesized that Hsf1 plays a role in cell migration, a process necessary for metastases. Using a cell culture model of migration in a scratch, we found that immortalized MEF cells derived from hsf1-/- animals were deficient in both basal and EGF-induced migration. MEF cell migration was dependent on JNK and ERK signaling, since inhibition of these pathways blocked EGF-stimulated cell migration. ERK was activated at the edge of the scratch in parental cells, and this activity was further increased after addition of EGF. Both basal and EGF-stimulated ERK activation were suppressed in hsf1-/- cells at the edge of the scratch. Furthermore, activation of ERK and JNK pathways by EGF was reduced in hsf1-/- cells. The impairment of MAP kinase signaling in hsf1-/- cells was partly due to the reduced expression of EGFR1. In addition, knockout of Hsf1 gene caused a second defect in MAP kinase signaling probably at the level of Ras. We conclude that HSF1 is necessary for MAP kinase signaling which in turn affects the EGF-induced cell migration.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Cornelia
authors.initials: C
authors.lastname: O'Callaghan-Sunol
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Sherman
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts; D017353:Gene Deletion; D000076249:Heat Shock Transcription Factors; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases