title: Role of ATF5 in the invasive potential of diverse human cancer cell lines.
abstract: Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element-binding protein family. Our research group recently revealed that ATF5 expression increases the invasiveness of human lung carcinoma cells. However, the effects of ATF5 on the invasive potential of other cancer cells lines remain unclear. Therefore, in this study, we investigated the role of ATF5 in the invasive activity of diverse human cancer cell lines. Invasiveness was assessed using Matrigel invasion assays. ATF5 knockdown resulted in decreased invasiveness in seven of eight cancer cell lines tested. These results suggest that ATF5 promotes invasiveness in several cancer cell lines. Furthermore, the roles of ATF5 in the invasiveness were evaluated in three-dimensional (3D) culture conditions. In 3D collagen gel, HT-1080 and MDA-MB-231 cells exhibited high invasiveness, with spindle morphology and high invasion speed. In both cell lines, knockdown of ATF5 resulted in rounded morphology and decreased invasion speed. Next, we showed that ATF5 induced integrin-α2 and integrin-β1 expression and that the depletion of integrin-α2 or integrin-β1 resulted in round morphology and decreased invasion speed. Our results suggest that ATF5 promotes invasion by inducing the expression of integrin-α2 and integrin-β1 in several human cancer cell lines.
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo, 060-0810, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nukuda
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo, 060-0810, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Endoh
authors.affiliation: Departmrnt of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, N13-W7, Kita-ku, Sapporo, 060-8586, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo, 060-0810, Japan.
authors.forename: Takeomi
authors.initials: T
authors.lastname: Mizutani
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo, 060-0810, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kawabata
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo, 060-0810, Japan. Electronic address: haga@sci.hokudai.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Haga
mesh_terms: D051696:Activating Transcription Factors / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C507532:ATF5 protein, human; D051696:Activating Transcription Factors; D018821:CD18 Antigens; D039421:Integrin alpha2
keywords: Activating transcription factor 5; Integrin-α2; Integrin-β1; Invasion; Spindle morphology