Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway
Gremlin-1 (GREM1), one of the bone morphogenetic protein (BMP) antagonists, can directly bind to BMPs. GREM1 is involved in organogenesis, tissue differentiation, and organ fibrosis. Recently, numerous studies have reported the oncogenic role of GREM1 in cancer. However, the role of GREM1 in metasta...
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| Veröffentlicht in: | International journal of molecular sciences 2020-12, Vol.21 (23), p.9227 |
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| creator | Sung, Nam Ji Kim, Na Hui Surh, Young-Joon Park, Sin-Aye |
| description | Gremlin-1 (GREM1), one of the bone morphogenetic protein (BMP) antagonists, can directly bind to BMPs. GREM1 is involved in organogenesis, tissue differentiation, and organ fibrosis. Recently, numerous studies have reported the oncogenic role of GREM1 in cancer. However, the role of GREM1 in metastasis of breast cancer cells and its underlying mechanisms remain poorly understood. The role of GREM1 in breast cancer progression was assessed by measuring growth, migration, and invasion of breast cancer cells. An orthotopic breast cancer mouse model was used to investigate the role of GREM1 in lung metastasis of breast cancer cells.
knockdown suppressed the proliferation of breast cancer cells, while its overexpression increased their growth, migration, and invasion. Cells with
-knockdown showed much lower tumor growth rates and lung metastasis than control cells. GREM1 enhanced the expression of matrix metalloproteinase 13 (MMP13). A positive correlation between
and
expression was observed in breast cancer patients. GREM1 activated signal transducer and activator of transcription 3 (STAT3) transcription factor involved in the expression of MMP13. Our study suggests that GREM1 can promote lung metastasis of breast cancer cells through the STAT3-MMP13 pathway. In addition, GREM1 might be a promising therapeutic target for breast cancer metastasis. |
| doi_str_mv | 10.3390/ijms21239227 |
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knockdown suppressed the proliferation of breast cancer cells, while its overexpression increased their growth, migration, and invasion. Cells with
-knockdown showed much lower tumor growth rates and lung metastasis than control cells. GREM1 enhanced the expression of matrix metalloproteinase 13 (MMP13). A positive correlation between
and
expression was observed in breast cancer patients. GREM1 activated signal transducer and activator of transcription 3 (STAT3) transcription factor involved in the expression of MMP13. Our study suggests that GREM1 can promote lung metastasis of breast cancer cells through the STAT3-MMP13 pathway. In addition, GREM1 might be a promising therapeutic target for breast cancer metastasis.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21239227</identifier><identifier>PMID: 33287358</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angiogenesis ; Animals ; Biomarkers ; Bone morphogenetic proteins ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Cell adhesion & migration ; Cell growth ; Cell Movement ; Cell Proliferation ; Collagenase 3 ; Differentiation (biology) ; Extracellular matrix ; Female ; Fibrosis ; Gene Expression Regulation, Neoplastic ; Gremlin protein ; Growth rate ; Humans ; Intercellular Signaling Peptides and Proteins - genetics ; Intercellular Signaling Peptides and Proteins - metabolism ; Lung cancer ; Lung Neoplasms - secondary ; Lungs ; Matrix metalloproteinase ; Matrix Metalloproteinase 13 - genetics ; Matrix Metalloproteinase 13 - metabolism ; Matrix metalloproteinases ; Metalloproteinase ; Metastases ; Metastasis ; Mice ; Organogenesis ; Prognosis ; Proteins ; Signal Transduction ; Stat3 protein ; STAT3 Transcription Factor - metabolism ; Tumors</subject><ispartof>International journal of molecular sciences, 2020-12, Vol.21 (23), p.9227</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-e660eadaf1e012b8a90df13dbf039085b35c6e1870dd76437f7c255c7a94ed9d3</citedby><cites>FETCH-LOGICAL-c478t-e660eadaf1e012b8a90df13dbf039085b35c6e1870dd76437f7c255c7a94ed9d3</cites><orcidid>0000-0003-2456-3572</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730512/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730512/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33287358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sung, Nam Ji</creatorcontrib><creatorcontrib>Kim, Na Hui</creatorcontrib><creatorcontrib>Surh, Young-Joon</creatorcontrib><creatorcontrib>Park, Sin-Aye</creatorcontrib><title>Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Gremlin-1 (GREM1), one of the bone morphogenetic protein (BMP) antagonists, can directly bind to BMPs. GREM1 is involved in organogenesis, tissue differentiation, and organ fibrosis. Recently, numerous studies have reported the oncogenic role of GREM1 in cancer. However, the role of GREM1 in metastasis of breast cancer cells and its underlying mechanisms remain poorly understood. The role of GREM1 in breast cancer progression was assessed by measuring growth, migration, and invasion of breast cancer cells. An orthotopic breast cancer mouse model was used to investigate the role of GREM1 in lung metastasis of breast cancer cells.
knockdown suppressed the proliferation of breast cancer cells, while its overexpression increased their growth, migration, and invasion. Cells with
-knockdown showed much lower tumor growth rates and lung metastasis than control cells. GREM1 enhanced the expression of matrix metalloproteinase 13 (MMP13). A positive correlation between
and
expression was observed in breast cancer patients. GREM1 activated signal transducer and activator of transcription 3 (STAT3) transcription factor involved in the expression of MMP13. Our study suggests that GREM1 can promote lung metastasis of breast cancer cells through the STAT3-MMP13 pathway. In addition, GREM1 might be a promising therapeutic target for breast cancer metastasis.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Bone morphogenetic proteins</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Collagenase 3</subject><subject>Differentiation (biology)</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gremlin protein</subject><subject>Growth rate</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - secondary</subject><subject>Lungs</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 13 - genetics</subject><subject>Matrix Metalloproteinase 13 - metabolism</subject><subject>Matrix metalloproteinases</subject><subject>Metalloproteinase</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Organogenesis</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Signal Transduction</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Tumors</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpVUVtPwjAYbYxGEH3z2TTx1Wkv27q9mOCiaAKRBHyuXddBybZiWzD8e4cgweRLvtvJ-S4HgGuM7ilN0YNe1I5gQlNC2Ano4pCQAKGYnR7FHXDh3AIhQkmUnoMOpSRhNEq64HNgVV3pJsBwbE1tvHJwpLxwrWkHTQmfrGozmIlGKgszVVUO5hvYl16vhdfNDE6m_SkNRqMxpnCiZ42ottWx8PNvsbkEZ6WonLra-x74eHmeZq_B8H3wlvWHgQxZ4gMVx0iJQpRYIUzyRKSoKDEt8hK1RyZRTiMZK5wwVBQsDikrmSRRJJlIQ1WkBe2Bxx3vcpXXqpCq8VZUfGl1LeyGG6H5_06j53xm1pwxiqL2fz1wuyew5mulnOcLs7LtMY6TME7aregv6m6HktY4Z1V5mIAR3-rBj_Vo4TfHWx3AfwLQH1iEhn0</recordid><startdate>20201203</startdate><enddate>20201203</enddate><creator>Sung, Nam Ji</creator><creator>Kim, Na Hui</creator><creator>Surh, Young-Joon</creator><creator>Park, Sin-Aye</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2456-3572</orcidid></search><sort><creationdate>20201203</creationdate><title>Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway</title><author>Sung, Nam Ji ; Kim, Na Hui ; Surh, Young-Joon ; Park, Sin-Aye</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-e660eadaf1e012b8a90df13dbf039085b35c6e1870dd76437f7c255c7a94ed9d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Bone morphogenetic proteins</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell adhesion & migration</topic><topic>Cell growth</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Collagenase 3</topic><topic>Differentiation (biology)</topic><topic>Extracellular matrix</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gremlin protein</topic><topic>Growth rate</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - secondary</topic><topic>Lungs</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 13 - genetics</topic><topic>Matrix Metalloproteinase 13 - metabolism</topic><topic>Matrix metalloproteinases</topic><topic>Metalloproteinase</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Organogenesis</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Signal Transduction</topic><topic>Stat3 protein</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sung, Nam Ji</creatorcontrib><creatorcontrib>Kim, Na Hui</creatorcontrib><creatorcontrib>Surh, Young-Joon</creatorcontrib><creatorcontrib>Park, Sin-Aye</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sung, Nam Ji</au><au>Kim, Na Hui</au><au>Surh, Young-Joon</au><au>Park, Sin-Aye</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-12-03</date><risdate>2020</risdate><volume>21</volume><issue>23</issue><spage>9227</spage><pages>9227-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Gremlin-1 (GREM1), one of the bone morphogenetic protein (BMP) antagonists, can directly bind to BMPs. GREM1 is involved in organogenesis, tissue differentiation, and organ fibrosis. Recently, numerous studies have reported the oncogenic role of GREM1 in cancer. However, the role of GREM1 in metastasis of breast cancer cells and its underlying mechanisms remain poorly understood. The role of GREM1 in breast cancer progression was assessed by measuring growth, migration, and invasion of breast cancer cells. An orthotopic breast cancer mouse model was used to investigate the role of GREM1 in lung metastasis of breast cancer cells.
knockdown suppressed the proliferation of breast cancer cells, while its overexpression increased their growth, migration, and invasion. Cells with
-knockdown showed much lower tumor growth rates and lung metastasis than control cells. GREM1 enhanced the expression of matrix metalloproteinase 13 (MMP13). A positive correlation between
and
expression was observed in breast cancer patients. GREM1 activated signal transducer and activator of transcription 3 (STAT3) transcription factor involved in the expression of MMP13. Our study suggests that GREM1 can promote lung metastasis of breast cancer cells through the STAT3-MMP13 pathway. In addition, GREM1 might be a promising therapeutic target for breast cancer metastasis.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33287358</pmid><doi>10.3390/ijms21239227</doi><orcidid>https://orcid.org/0000-0003-2456-3572</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Animals Biomarkers Bone morphogenetic proteins Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - mortality Breast Neoplasms - pathology Cell adhesion & migration Cell growth Cell Movement Cell Proliferation Collagenase 3 Differentiation (biology) Extracellular matrix Female Fibrosis Gene Expression Regulation, Neoplastic Gremlin protein Growth rate Humans Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - metabolism Lung cancer Lung Neoplasms - secondary Lungs Matrix metalloproteinase Matrix Metalloproteinase 13 - genetics Matrix Metalloproteinase 13 - metabolism Matrix metalloproteinases Metalloproteinase Metastases Metastasis Mice Organogenesis Prognosis Proteins Signal Transduction Stat3 protein STAT3 Transcription Factor - metabolism Tumors |
| title | Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway |
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