WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4

Abstract WAVE2 is a member of the WASP/WAVE family of actin cytoskeletal regulatory proteins; unfortunately, little is known about its function in pancreatic cancers. In this study, we report the role of WAVE2 in the motility and invasiveness of pancreatic cancer cells. High WAVE2 expression in huma...

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Main Authors: Keisuke Taniuchi, Mutsuo Furihata, Seiji Naganuma, Toshiji Saibara
Format: Article
Language:English
Published: Wiley 2018-11-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.1837
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author Keisuke Taniuchi
Mutsuo Furihata
Seiji Naganuma
Toshiji Saibara
author_facet Keisuke Taniuchi
Mutsuo Furihata
Seiji Naganuma
Toshiji Saibara
author_sort Keisuke Taniuchi
collection DOAJ
description Abstract WAVE2 is a member of the WASP/WAVE family of actin cytoskeletal regulatory proteins; unfortunately, little is known about its function in pancreatic cancers. In this study, we report the role of WAVE2 in the motility and invasiveness of pancreatic cancer cells. High WAVE2 expression in human pancreatic cancer tissues was correlated with overall survival. WAVE2 accumulated in the cell protrusions of pancreatic cancer cell lines. Downregulation of WAVE2 by small interfering RNA decreased the cell protrusions and inhibited the motility and invasiveness of pancreatic cancer cells. WAVE2 promoted pancreatic cancer cell motility and invasion by forming a complex with the actin cytoskeletal protein alpha‐actinin 4 (ACTN4). Downregulation of ACTN4 by small interfering RNA also inhibited the motility and invasiveness of the cells through a decrease in cell protrusions. Further investigation showed that WAVE2/ACTN4 signaling selectively stimulated p27 phosphorylation and thereby increased the motility and invasiveness of the cells. These results suggest that WAVE2 and ACTN4 stimulate p27 phosphorylation and provide evidence that WAVE2 promotes the motility and invasiveness of pancreatic cancer cells.
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spelling doaj.art-af80c4bba28345dfbbd3e58da09a1c732023-09-19T11:30:57ZengWileyCancer Medicine2045-76342018-11-017115733575110.1002/cam4.1837WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4Keisuke Taniuchi0Mutsuo Furihata1Seiji Naganuma2Toshiji Saibara3Department of Gastroenterology and Hepatology, Kochi Medical School Kochi University Kochi JapanDepartment of Pathology, Kochi Medical School Kochi University Kochi JapanDepartment of Pathology, Kochi Medical School Kochi University Kochi JapanDepartment of Gastroenterology and Hepatology, Kochi Medical School Kochi University Kochi JapanAbstract WAVE2 is a member of the WASP/WAVE family of actin cytoskeletal regulatory proteins; unfortunately, little is known about its function in pancreatic cancers. In this study, we report the role of WAVE2 in the motility and invasiveness of pancreatic cancer cells. High WAVE2 expression in human pancreatic cancer tissues was correlated with overall survival. WAVE2 accumulated in the cell protrusions of pancreatic cancer cell lines. Downregulation of WAVE2 by small interfering RNA decreased the cell protrusions and inhibited the motility and invasiveness of pancreatic cancer cells. WAVE2 promoted pancreatic cancer cell motility and invasion by forming a complex with the actin cytoskeletal protein alpha‐actinin 4 (ACTN4). Downregulation of ACTN4 by small interfering RNA also inhibited the motility and invasiveness of the cells through a decrease in cell protrusions. Further investigation showed that WAVE2/ACTN4 signaling selectively stimulated p27 phosphorylation and thereby increased the motility and invasiveness of the cells. These results suggest that WAVE2 and ACTN4 stimulate p27 phosphorylation and provide evidence that WAVE2 promotes the motility and invasiveness of pancreatic cancer cells.https://doi.org/10.1002/cam4.1837actin cytoskeletonACTN4cell invasionp27pancreatic cancerWAVE2
spellingShingle Keisuke Taniuchi
Mutsuo Furihata
Seiji Naganuma
Toshiji Saibara
WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4
Cancer Medicine
actin cytoskeleton
ACTN4
cell invasion
p27
pancreatic cancer
WAVE2
title WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4
title_full WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4
title_fullStr WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4
title_full_unstemmed WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4
title_short WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4
title_sort wave2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to actn4
topic actin cytoskeleton
ACTN4
cell invasion
p27
pancreatic cancer
WAVE2
url https://doi.org/10.1002/cam4.1837
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AT seijinaganuma wave2isassociatedwithpoorprognosisinpancreaticcancersandpromotescellmotilityandinvasivenessviabindingtoactn4
AT toshijisaibara wave2isassociatedwithpoorprognosisinpancreaticcancersandpromotescellmotilityandinvasivenessviabindingtoactn4