title: Active heat shock transcription factor 1 supports migration of the melanoma cells via vinculin down-regulation.
abstract: Heat shock transcription factor 1 (HSF1), the major regulator of stress response, is frequently activated in cancer and has an apparent role in malignant transformation. Here we analyzed the influence of the over-expression of a constitutively active transcriptionally-competent HSF1 mutant form on phenotypes of mouse and human melanoma cells. We observed that the expression of active HSF1 supported anchorage-independent growth in vitro, and metastatic spread in the animal model in vivo, although the proliferation rate of cancer cells was not affected. Furthermore, active HSF1 enhanced cell motility, reduced the adherence of cells to a fibronectin-coated surface, and affected the actin cytoskeleton. We found that although the expression of active HSF1 did not affect levels of epithelial-to-mesenchymal transition markers, it caused transcriptional down-regulation of vinculin, protein involved in cell motility, and adherence. Functional HSF1-binding sites were found in mouse and human Vcl/VCL genes, indicating a direct role of HSF1 in the regulation of this gene. An apparent association between HSF1-induced down-regulation of vinculin, increased motility, and a reduced adherence of cells suggests a possible mechanism of HSF1-mediated enhancement of the metastatic potential of cancer cells.
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. Electronic address: agatoma5@wp.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Toma-Jonik
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. Electronic address: wwidlak@io.gliwice.pl.
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Widlak
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. Electronic address: joanna1540@op.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Korfanty
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. Electronic address: tcichon@io.gliwice.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Cichon
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. Electronic address: rsmolarczyk@io.gliwice.pl.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Smolarczyk
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. Electronic address: agogler@io.gliwice.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gogler-Piglowska
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. Electronic address: widlak@io.gliwice.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Widlak
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland. Electronic address: nvydra@yahoo.co.uk.
authors.forename: Natalia
authors.initials: N
authors.lastname: Vydra
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013696:Temperature; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014184:Transplantation, Homologous; D016596:Vinculin / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D016596:Vinculin
keywords: Adhesion; Anchorage-independent growth; Metastasis; Thermotolerance; Vinculin