Tankyrase-Binding Protein TNKS1BP1 Regulates Actin Cytoskeleton Rearrangement and Cancer Cell Invasion.
Cancer Res
; 77(9): 2328-2338, 2017 05 01.
Article
in En
| MEDLINE
| ID: mdl-28202517
ABSTRACT
Tankyrase, a PARP that promotes telomere elongation and Wnt/ß-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Actin Cytoskeleton
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Telomeric Repeat Binding Protein 1
/
Neoplasm Invasiveness
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Cancer Res
Year:
2017
Document type:
Article
Affiliation country:
Japón