Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.

Collagen XVII (COL17), a cell-matrix adhesion protein, has been found to be suppressed in breast cancer. Our previous data demonstrated a preventive role of COL17 in breast cancer invasiveness. The present study used the stable COL17-overexpressing MCF7 and MDA-MB-231 cells to reveal an anti-prolife...

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Autores principales:	Muttarin Lothong, Watchara Sakares, Pornchai Rojsitthisak, Chizu Tanikawa, Koichi Matsuda, Varalee Yodsurang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2731ce70639c48b587ebf373b27a6fd0
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spelling	oai:doaj.org-article:2731ce70639c48b587ebf373b27a6fd02021-12-02T20:04:56ZCollagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.1932-620310.1371/journal.pone.0255179https://doaj.org/article/2731ce70639c48b587ebf373b27a6fd02021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255179https://doaj.org/toc/1932-6203Collagen XVII (COL17), a cell-matrix adhesion protein, has been found to be suppressed in breast cancer. Our previous data demonstrated a preventive role of COL17 in breast cancer invasiveness. The present study used the stable COL17-overexpressing MCF7 and MDA-MB-231 cells to reveal an anti-proliferative effect of COL17 on breast cancer cell through mTOR deactivation. Cell proliferation was negatively correlated with the expression level of COL17 in a concentration-dependent manner in both conventional and three-dimensional (3D) culture systems. The correlation was confirmed by decreased expression of the proliferative marker Ki67 in COL17-expressing cells. In addition, overexpression of COL17 reduced the clonogenicity and growth of the cells. We demonstrated that COL17 affects the AKT/mTOR signaling pathway by deactivation of AKT, mTOR and downstream effectors, particularly 4EBP1. Moreover, mice xenografted with high COL17-expressing cells exhibited delayed tumor progression and prolonged survival time. The high expression of COL17A1 gene encoding COL17 is associated with low-proliferation tumors, extended tumor-free period, and overall survival of breast cancer patients. In conclusion, our results revealed the novel function of COL17 using in vitro and in vivo models and elucidated the related pathway in breast cancer cell growth and proliferation.Muttarin LothongWatchara SakaresPornchai RojsitthisakChizu TanikawaKoichi MatsudaVaralee YodsurangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0255179 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muttarin Lothong Watchara Sakares Pornchai Rojsitthisak Chizu Tanikawa Koichi Matsuda Varalee Yodsurang Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.
description	Collagen XVII (COL17), a cell-matrix adhesion protein, has been found to be suppressed in breast cancer. Our previous data demonstrated a preventive role of COL17 in breast cancer invasiveness. The present study used the stable COL17-overexpressing MCF7 and MDA-MB-231 cells to reveal an anti-proliferative effect of COL17 on breast cancer cell through mTOR deactivation. Cell proliferation was negatively correlated with the expression level of COL17 in a concentration-dependent manner in both conventional and three-dimensional (3D) culture systems. The correlation was confirmed by decreased expression of the proliferative marker Ki67 in COL17-expressing cells. In addition, overexpression of COL17 reduced the clonogenicity and growth of the cells. We demonstrated that COL17 affects the AKT/mTOR signaling pathway by deactivation of AKT, mTOR and downstream effectors, particularly 4EBP1. Moreover, mice xenografted with high COL17-expressing cells exhibited delayed tumor progression and prolonged survival time. The high expression of COL17A1 gene encoding COL17 is associated with low-proliferation tumors, extended tumor-free period, and overall survival of breast cancer patients. In conclusion, our results revealed the novel function of COL17 using in vitro and in vivo models and elucidated the related pathway in breast cancer cell growth and proliferation.
format	article
author	Muttarin Lothong Watchara Sakares Pornchai Rojsitthisak Chizu Tanikawa Koichi Matsuda Varalee Yodsurang
author_facet	Muttarin Lothong Watchara Sakares Pornchai Rojsitthisak Chizu Tanikawa Koichi Matsuda Varalee Yodsurang
author_sort	Muttarin Lothong
title	Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.
title_short	Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.
title_full	Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.
title_fullStr	Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.
title_full_unstemmed	Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.
title_sort	collagen xvii inhibits breast cancer cell proliferation and growth through deactivation of the akt/mtor signaling pathway.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2731ce70639c48b587ebf373b27a6fd0
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Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.

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