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Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton

Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-bind...

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Autores principales: Qin, Juan, Li, Dengwen, Zhou, Yunqiang, Xie, Songbo, Du, Xin, Hao, Ziwei, Liu, Ruming, Liu, Xinqi, Liu, Min, Zhou, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356838/
https://www.ncbi.nlm.nih.gov/pubmed/27926525
http://dx.doi.org/10.18632/oncotarget.13740
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author Qin, Juan
Li, Dengwen
Zhou, Yunqiang
Xie, Songbo
Du, Xin
Hao, Ziwei
Liu, Ruming
Liu, Xinqi
Liu, Min
Zhou, Jun
author_facet Qin, Juan
Li, Dengwen
Zhou, Yunqiang
Xie, Songbo
Du, Xin
Hao, Ziwei
Liu, Ruming
Liu, Xinqi
Liu, Min
Zhou, Jun
author_sort Qin, Juan
collection PubMed
description Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy. Our data further show that ALG-2 stimulates breast cancer growth and metastasis in mice. ALG-2 also promotes breast cancer cell proliferation, survival, and motility in vitro. Mechanistic data reveal that ALG-2 disrupts the localization of centrosome proteins, resulting in spindle multipolarity and chromosome missegregation. In addition, ALG-2 drives the polarization and migration of breast cancer cells by facilitating the rearrangement of microtubules and microfilaments. These findings reveal a critical role for ALG-2 in the pathogenesis of breast cancer and have important implications for its diagnosis and therapy.
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spelling pubmed-53568382017-04-20 Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton Qin, Juan Li, Dengwen Zhou, Yunqiang Xie, Songbo Du, Xin Hao, Ziwei Liu, Ruming Liu, Xinqi Liu, Min Zhou, Jun Oncotarget Research Paper Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy. Our data further show that ALG-2 stimulates breast cancer growth and metastasis in mice. ALG-2 also promotes breast cancer cell proliferation, survival, and motility in vitro. Mechanistic data reveal that ALG-2 disrupts the localization of centrosome proteins, resulting in spindle multipolarity and chromosome missegregation. In addition, ALG-2 drives the polarization and migration of breast cancer cells by facilitating the rearrangement of microtubules and microfilaments. These findings reveal a critical role for ALG-2 in the pathogenesis of breast cancer and have important implications for its diagnosis and therapy. Impact Journals LLC 2016-12-01 /pmc/articles/PMC5356838/ /pubmed/27926525 http://dx.doi.org/10.18632/oncotarget.13740 Text en Copyright: © 2017 Qin et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Qin, Juan
Li, Dengwen
Zhou, Yunqiang
Xie, Songbo
Du, Xin
Hao, Ziwei
Liu, Ruming
Liu, Xinqi
Liu, Min
Zhou, Jun
Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton
title Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton
title_full Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton
title_fullStr Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton
title_full_unstemmed Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton
title_short Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton
title_sort apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356838/
https://www.ncbi.nlm.nih.gov/pubmed/27926525
http://dx.doi.org/10.18632/oncotarget.13740
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