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Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β

Adenylate cyclase-associated protein 1 (CAP1) is an evolutionarily conserved protein that regulates actin dynamics. Our previous study indicates that CAP1 is overexpressed in NSCLC tissues and correlated with poor clinical outcomes. Further establishing the role and dissecting underlying mechanisms...

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Autores principales: Xie, Shuanshuan, Liu, Yang, Li, Xuan, Tan, Min, Wang, Changhui, Field, Jeffrey, Zhou, Guo-Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096378/
https://www.ncbi.nlm.nih.gov/pubmed/30123351
http://dx.doi.org/10.7150/jca.25993
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author Xie, Shuanshuan
Liu, Yang
Li, Xuan
Tan, Min
Wang, Changhui
Field, Jeffrey
Zhou, Guo-Lei
author_facet Xie, Shuanshuan
Liu, Yang
Li, Xuan
Tan, Min
Wang, Changhui
Field, Jeffrey
Zhou, Guo-Lei
author_sort Xie, Shuanshuan
collection PubMed
description Adenylate cyclase-associated protein 1 (CAP1) is an evolutionarily conserved protein that regulates actin dynamics. Our previous study indicates that CAP1 is overexpressed in NSCLC tissues and correlated with poor clinical outcomes. Further establishing the role and dissecting underlying mechanisms are imperative before targeting CAP1 can become a possibility for cancer treatment. Here we report our findings that knockdown of CAP1 inhibited cell proliferation and induced apoptosis in vitro and in vivo. Moreover, phosphor mutants of CAP1 at the S307/S309 regulatory site had compromised rescue effects for both the invasiveness and the proliferation in CAP1-knockdown cells and GSK3β kinase inhibitor LiCl inhibited cell phosphorylation site S307/S309 by up-regulating the expression of p53, BAK, BAD and cleaved PARP induced ROS production, decreased lung cancer cell viability, adhesion, proliferation, migration and invasion, and induction of apoptosis. These novel mechanistic insights may ultimately open up avenues for strategies targeting CAP1 in the treatment of lung cancer, tailored for specific types of the highly diverse disease.
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spelling pubmed-60963782018-08-17 Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β Xie, Shuanshuan Liu, Yang Li, Xuan Tan, Min Wang, Changhui Field, Jeffrey Zhou, Guo-Lei J Cancer Research Paper Adenylate cyclase-associated protein 1 (CAP1) is an evolutionarily conserved protein that regulates actin dynamics. Our previous study indicates that CAP1 is overexpressed in NSCLC tissues and correlated with poor clinical outcomes. Further establishing the role and dissecting underlying mechanisms are imperative before targeting CAP1 can become a possibility for cancer treatment. Here we report our findings that knockdown of CAP1 inhibited cell proliferation and induced apoptosis in vitro and in vivo. Moreover, phosphor mutants of CAP1 at the S307/S309 regulatory site had compromised rescue effects for both the invasiveness and the proliferation in CAP1-knockdown cells and GSK3β kinase inhibitor LiCl inhibited cell phosphorylation site S307/S309 by up-regulating the expression of p53, BAK, BAD and cleaved PARP induced ROS production, decreased lung cancer cell viability, adhesion, proliferation, migration and invasion, and induction of apoptosis. These novel mechanistic insights may ultimately open up avenues for strategies targeting CAP1 in the treatment of lung cancer, tailored for specific types of the highly diverse disease. Ivyspring International Publisher 2018-07-16 /pmc/articles/PMC6096378/ /pubmed/30123351 http://dx.doi.org/10.7150/jca.25993 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Xie, Shuanshuan
Liu, Yang
Li, Xuan
Tan, Min
Wang, Changhui
Field, Jeffrey
Zhou, Guo-Lei
Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β
title Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β
title_full Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β
title_fullStr Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β
title_full_unstemmed Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β
title_short Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β
title_sort phosphorylation of the cytoskeletal protein cap1 regulates non-small cell lung cancer survival and proliferation by gsk3β
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096378/
https://www.ncbi.nlm.nih.gov/pubmed/30123351
http://dx.doi.org/10.7150/jca.25993
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