title: Tankyrase-Binding Protein TNKS1BP1 Regulates Actin Cytoskeleton Rearrangement and Cancer Cell Invasion.
abstract: Tankyrase, a PARP that promotes telomere elongation and Wnt/β-catenin signaling, has various binding partners, suggesting that it has as-yet unidentified functions. Here, we report that the tankyrase-binding protein TNKS1BP1 regulates actin cytoskeleton and cancer cell invasion, which is closely associated with cancer progression. TNKS1BP1 colocalized with actin filaments and negatively regulated cell invasion. In TNKS1BP1-depleted cells, actin filament dynamics, focal adhesion, and lamellipodia ruffling were increased with activation of the ROCK/LIMK/cofilin pathway. TNKS1BP1 bound the actin-capping protein CapZA2. TNKS1BP1 depletion dissociated CapZA2 from the cytoskeleton, leading to cofilin phosphorylation and enhanced cell invasion. Tankyrase overexpression increased cofilin phosphorylation, dissociated CapZA2 from cytoskeleton, and enhanced cell invasion in a PARP activity-dependent manner. In clinical samples of pancreatic cancer, TNKS1BP1 expression was reduced in invasive regions. We propose that the tankyrase-TNKS1BP1 axis constitutes a posttranslational modulator of cell invasion whose aberration promotes cancer malignancy.Cancer Res; 77(9); 2328-38. ©2017 AACR.
authors.affiliation: Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.|Institute of Microbial Chemistry (BIKAKEN), Numazu, Numazu-shi, Shizuoka, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ohishi
authors.affiliation: Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Divison of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Katori
authors.affiliation: Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Migita
authors.affiliation: Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Muramatsu
authors.affiliation: Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Divison of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Saiura
authors.affiliation: Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo, Japan.
authors.forename: Shun-Ichiro
authors.initials: SI
authors.lastname: Iemura
authors.affiliation: Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.affiliation: Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan. hseimiya@jfcr.or.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seimiya
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics* / Q000473:pathology; D051339:Actin Depolymerizing Factors / Q000235:genetics; D051347:CapZ Actin Capping Protein / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D022001:Focal Adhesions / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D054461:Lim Kinases / Q000235:genetics; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics; D035321:Telomeric Repeat Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D060449:Wnt Signaling Pathway; D054460:rho-Associated Kinases / Q000235:genetics
chemical_list: D051339:Actin Depolymerizing Factors; C495845:CAPZA2 protein, human; D051347:CapZ Actin Capping Protein; C455625:TNKS1BP1 protein, human; D035321:Telomeric Repeat Binding Protein 1; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; C515892:LIMK1 protein, human; D054461:Lim Kinases; D054460:rho-Associated Kinases