title: Heat shock factor 1 is required for migration and invasion of human melanoma in vitro and in vivo.
abstract: Heat shock factor 1 (HSF1) is a major transactivator of the heat shock response. Recent studies have demonstrated that HSF1 is involved in tumor initiation, maintenance, and progression by regulating the expression of heat shock proteins (HSPs) and other molecular targets. Furthermore, HSF1 was identified as a potent proinvasion oncogene in human melanomas. However, the biological functions of HSF1 in human melanoma remain poorly understood. To determine the functional role of HSF1 in melanoma, we used short hairpin RNA (shRNA) to silence HSF1 in human melanoma cell lines and investigated its effect on cell migration and invasive ability in vitro. We found that HSF1 knockdown led to a marked reduction in migration and invasive ability, and these functions were restored by overexpression of wild-type HSF1. To confirm the in vitro results, we performed subcutaneous xenograft experiments in athymic nude mice. We found that HSF1 was required for melanoma invasion and metastasis, as well as tumorigenic potential in vivo. Overall, these results show that HSF1 is indispensable for melanoma progression and metastasis, and suggests that HSF1 could be a promising therapeutic target for melanoma.
authors.affiliation: Department of Dermatology, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: naka629@yamaguchi-u.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Dermatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Sonoko
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Dermatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashida
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takii
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Takaki
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.affiliation: Department of Dermatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Muto
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D034741:RNA, Small Interfering; D014157:Transcription Factors
keywords: Heat shock factor 1 (HSF1); Invasion; Malignant melanoma; Metastasis; Migration