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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| 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. |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0255179</identifier><identifier>PMID: 34293053</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AKT protein ; Antibiotics ; Apoptosis ; Autoantigens - genetics ; Autoantigens - metabolism ; Biology and Life Sciences ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Care and treatment ; Cell culture ; Cell growth ; Cell proliferation ; Cell Proliferation - drug effects ; Clone Cells ; Collagen ; Collagen Type XVII ; Deactivation ; Disease Progression ; DNA methylation ; Doxycycline - pharmacology ; Extracellular matrix ; Female ; Gastrointestinal cancer ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Genetic aspects ; Genomes ; Health aspects ; Humans ; Invasiveness ; Ki-67 Antigen - metabolism ; Laboratories ; Medicine and Health Sciences ; Models, Biological ; Multivariate Analysis ; Non-Fibrillar Collagens - genetics ; Non-Fibrillar Collagens - metabolism ; Pharmaceutical sciences ; Pharmacology ; Physiology ; Proportional Hazards Models ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction ; Signaling ; Skin ; Spheroids, Cellular - drug effects ; Spheroids, Cellular - pathology ; Survival ; Survival Analysis ; TOR protein ; TOR Serine-Threonine Kinases - metabolism ; Tumors ; Xenografts</subject><ispartof>PloS one, 2021-07, Vol.16 (7), p.e0255179</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Lothong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>AKT protein</subject><subject>Antibiotics</subject><subject>Apoptosis</subject><subject>Autoantigens - genetics</subject><subject>Autoantigens - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Care and treatment</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Clone Cells</subject><subject>Collagen</subject><subject>Collagen Type XVII</subject><subject>Deactivation</subject><subject>Disease Progression</subject><subject>DNA methylation</subject><subject>Doxycycline - pharmacology</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Gastrointestinal cancer</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34293053</pmid><doi>10.1371/journal.pone.0255179</doi><tpages>e0255179</tpages><orcidid>https://orcid.org/0000-0002-3622-532X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | AKT protein Antibiotics Apoptosis Autoantigens - genetics Autoantigens - metabolism Biology and Life Sciences Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Care and treatment Cell culture Cell growth Cell proliferation Cell Proliferation - drug effects Clone Cells Collagen Collagen Type XVII Deactivation Disease Progression DNA methylation Doxycycline - pharmacology Extracellular matrix Female Gastrointestinal cancer Gene expression Gene Expression Regulation, Neoplastic - drug effects Genetic aspects Genomes Health aspects Humans Invasiveness Ki-67 Antigen - metabolism Laboratories Medicine and Health Sciences Models, Biological Multivariate Analysis Non-Fibrillar Collagens - genetics Non-Fibrillar Collagens - metabolism Pharmaceutical sciences Pharmacology Physiology Proportional Hazards Models Proteins Proto-Oncogene Proteins c-akt - metabolism Signal Transduction Signaling Skin Spheroids, Cellular - drug effects Spheroids, Cellular - pathology Survival Survival Analysis TOR protein TOR Serine-Threonine Kinases - metabolism Tumors Xenografts |
| title | Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T06%3A59%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Collagen%20XVII%20inhibits%20breast%20cancer%20cell%20proliferation%20and%20growth%20through%20deactivation%20of%20the%20AKT/mTOR%20signaling%20pathway&rft.jtitle=PloS%20one&rft.au=Lothong,%20Muttarin&rft.date=2021-07-22&rft.volume=16&rft.issue=7&rft.spage=e0255179&rft.pages=e0255179-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0255179&rft_dat=%3Cgale_plos_%3EA669333908%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2554336787&rft_id=info:pmid/34293053&rft_galeid=A669333908&rft_doaj_id=oai_doaj_org_article_2731ce70639c48b587ebf373b27a6fd0&rfr_iscdi=true |