RRC ID 65880
Author Ohishi T, Yoshida H, Katori M, Migita T, Muramatsu Y, Miyake M, Ishikawa Y, Saiura A, Iemura SI, Natsume T, Seimiya H.
Title Tankyrase-Binding Protein TNKS1BP1 Regulates Actin Cytoskeleton Rearrangement and Cancer Cell Invasion.
Journal Cancer Res
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.
Volume 77(9)
Pages 2328-2338
Published 2017-5-1
DOI 10.1158/0008-5472.CAN-16-1846
PII 0008-5472.CAN-16-1846
PMID 28202517
MeSH Actin Cytoskeleton / genetics* Actin Cytoskeleton / pathology Actin Depolymerizing Factors / genetics CapZ Actin Capping Protein / genetics Cell Adhesion / genetics Cell Line, Tumor Female Focal Adhesions / genetics Gene Expression Regulation, Neoplastic Humans Lim Kinases / genetics Male Neoplasm Invasiveness / genetics* Neoplasm Invasiveness / pathology Pancreatic Neoplasms / genetics* Pancreatic Neoplasms / pathology Phosphorylation Poly (ADP-Ribose) Polymerase-1 / genetics Telomeric Repeat Binding Protein 1 / biosynthesis Telomeric Repeat Binding Protein 1 / genetics* Wnt Signaling Pathway rho-Associated Kinases / genetics
IF 9.727
Human and Animal Cells KLM-1(RCB2138) PANC-1(RCB2095)