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Brief Report
Heat Shock Transcription Factor HSF1 Plays a Critical Role in Cell Migration via Maintaining MAP Kinase Signaling
Cornelia O’Callaghan-Sunol and Michael Y. Sherman
volume 5 | issue 13
1 july 2006Pages: 1431 - 1437
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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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.