Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2
The extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-ind...
Gespeichert in:
| Veröffentlicht in: | Cell death & disease 2019-04, Vol.10 (5), p.341, Article 341 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 5 |
| container_start_page | 341 |
| container_title | Cell death & disease |
| container_volume | 10 |
| creator | Chen, Yan Chen, Lin Hong, Duanyang Chen, Zongyue Zhang, Jingyu Fu, Lingyun Pan, Di Zhang, Yanyan Xu, Yini Gan, Shiquan Xiao, Chaoda Tao, Ling Shen, Xiangchun |
| description | The extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial–mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced migration, invasion, and F-actin remodeling. Baicalein also suppressed FN-induced downregulation of the epithelial markers E-cadherin and ZO-1 and upregulation of the mesenchymal markers N-cadherin, vimentin, and Snail. Further investigation revealed that calpain-2 was involved in baicalein suppression of FN-induced EMT. Baicalein significantly decreased FN-enhanced calpain-2 expression and activation by suppressing its plasma membrane localization, substrate cleavage, and degradation of its endogenous inhibitor calpastatin. Overexpression of calpain-2 in MCF-10A cells by gene transfection partially blocked the inhibitory effect of baicalein on FN-induced EMT changes. In addition, baicalein inhibited calpain-2 by decreasing FN-increased intracellular calcium ion levels and extracellular signal-regulated protein kinases activation. Baicalein significantly decreased tumor onset, growth, and pulmonary metastasis in a spontaneous breast cancer MMTV-PyMT mouse model. Baicalein also reduced the expression of FN, calpain-2, and vimentin, but increased E-cadherin expression in MMTV-PyMT mouse tumors. Overall, these results revealed that baicalein markedly inhibited FN-induced EMT by inhibiting calpain-2, thus providing novel insights into the pharmacological action and mechanism of baicalein. Baicalein may therefore possess therapeutic potential for the treatment of breast cancer though interfering with extracellular matrix–cancer cell interactions. |
| doi_str_mv | 10.1038/s41419-019-1572-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6472504</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2211320268</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-2101ed12eb0cded7e6b16863e3b1a6d2649886ef0a8e7c9df3ea3470291e20a93</originalsourceid><addsrcrecordid>eNp1Uc1KHTEUDqWiYn0ANyXQ9dicZG5mZiNYqa0gdFPX4Uxy5t7I3Mw0mRHurn2GvqFPYuyotYsGQn7O9wcfYycgTkGo-mMqoYSmEHnDqpJF9YYdSlFCUdZ18_bV_YAdp3Qr8lJKyJXeZwcK8ks3-pD9-oTeYk8-cB82vvVT4p1v4xDITj4UPrjZkuM0-mlDvcf-_ufvLSUKdrPbYs-niCH5yQ-BtzvuyEbC5MOaY-bf4Z8BBsfnMdJ67pePoePZdMRsIN-xvQ77RMdP5xG7ufz8_eJrcf3ty9XF-XVhV0pPhQQB5EBSK6wjV5FuQddakWoBtZO6bOpaUyewpso2rlOEqqyEbICkwEYdsbNFd5zbLTlLIUfvzRj9FuPODOjNv5PgN2Y93BldVnIlyizw4UkgDj9mSpO5HeYYcmYjJYCSQuo6o2BB2TikFKl7cQBhHoszS3EmF2ceizNV5rx_He2F8VxTBsgFkPIorCn-tf6_6gMh_6hn</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2211320268</pqid></control><display><type>article</type><title>Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>PubMed Central</source><creator>Chen, Yan ; Chen, Lin ; Hong, Duanyang ; Chen, Zongyue ; Zhang, Jingyu ; Fu, Lingyun ; Pan, Di ; Zhang, Yanyan ; Xu, Yini ; Gan, Shiquan ; Xiao, Chaoda ; Tao, Ling ; Shen, Xiangchun</creator><creatorcontrib>Chen, Yan ; Chen, Lin ; Hong, Duanyang ; Chen, Zongyue ; Zhang, Jingyu ; Fu, Lingyun ; Pan, Di ; Zhang, Yanyan ; Xu, Yini ; Gan, Shiquan ; Xiao, Chaoda ; Tao, Ling ; Shen, Xiangchun</creatorcontrib><description>The extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial–mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced migration, invasion, and F-actin remodeling. Baicalein also suppressed FN-induced downregulation of the epithelial markers E-cadherin and ZO-1 and upregulation of the mesenchymal markers N-cadherin, vimentin, and Snail. Further investigation revealed that calpain-2 was involved in baicalein suppression of FN-induced EMT. Baicalein significantly decreased FN-enhanced calpain-2 expression and activation by suppressing its plasma membrane localization, substrate cleavage, and degradation of its endogenous inhibitor calpastatin. Overexpression of calpain-2 in MCF-10A cells by gene transfection partially blocked the inhibitory effect of baicalein on FN-induced EMT changes. In addition, baicalein inhibited calpain-2 by decreasing FN-increased intracellular calcium ion levels and extracellular signal-regulated protein kinases activation. Baicalein significantly decreased tumor onset, growth, and pulmonary metastasis in a spontaneous breast cancer MMTV-PyMT mouse model. Baicalein also reduced the expression of FN, calpain-2, and vimentin, but increased E-cadherin expression in MMTV-PyMT mouse tumors. Overall, these results revealed that baicalein markedly inhibited FN-induced EMT by inhibiting calpain-2, thus providing novel insights into the pharmacological action and mechanism of baicalein. Baicalein may therefore possess therapeutic potential for the treatment of breast cancer though interfering with extracellular matrix–cancer cell interactions.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-019-1572-7</identifier><identifier>PMID: 31000696</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/19 ; 631/154/436/2388 ; 64 ; 64/60 ; 692/308/153 ; 96/109 ; 96/31 ; Actin ; Animals ; Antibodies ; Biochemistry ; Biomedical and Life Sciences ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Butadienes - pharmacology ; Cadherins - metabolism ; Calcium (extracellular) ; Calcium (intracellular) ; Calcium - metabolism ; Calpain ; Calpain - metabolism ; Calpastatin ; Cell Biology ; Cell Culture ; Cell interactions ; Cell Line, Tumor ; E-cadherin ; Epithelial cells ; Epithelial-Mesenchymal Transition - drug effects ; Extracellular matrix ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Fibronectin ; Fibronectins - metabolism ; Flavanones - pharmacology ; Flavanones - therapeutic use ; Humans ; Immunology ; Kaplan-Meier Estimate ; Life Sciences ; Localization ; Matrix protein ; Mesenchyme ; Metastases ; Mice ; Mice, Transgenic ; N-Cadherin ; Nitriles - pharmacology ; Protein kinase ; Transfection ; Transgenic mice ; Tumorigenesis ; Up-regulation ; Up-Regulation - drug effects ; Vimentin ; Zonula occludens-1 protein ; Zonula Occludens-1 Protein - metabolism</subject><ispartof>Cell death & disease, 2019-04, Vol.10 (5), p.341, Article 341</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-2101ed12eb0cded7e6b16863e3b1a6d2649886ef0a8e7c9df3ea3470291e20a93</citedby><cites>FETCH-LOGICAL-c536t-2101ed12eb0cded7e6b16863e3b1a6d2649886ef0a8e7c9df3ea3470291e20a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472504/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472504/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,41101,42170,51557,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31000696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Yan</creatorcontrib><creatorcontrib>Chen, Lin</creatorcontrib><creatorcontrib>Hong, Duanyang</creatorcontrib><creatorcontrib>Chen, Zongyue</creatorcontrib><creatorcontrib>Zhang, Jingyu</creatorcontrib><creatorcontrib>Fu, Lingyun</creatorcontrib><creatorcontrib>Pan, Di</creatorcontrib><creatorcontrib>Zhang, Yanyan</creatorcontrib><creatorcontrib>Xu, Yini</creatorcontrib><creatorcontrib>Gan, Shiquan</creatorcontrib><creatorcontrib>Xiao, Chaoda</creatorcontrib><creatorcontrib>Tao, Ling</creatorcontrib><creatorcontrib>Shen, Xiangchun</creatorcontrib><title>Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>The extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial–mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced migration, invasion, and F-actin remodeling. Baicalein also suppressed FN-induced downregulation of the epithelial markers E-cadherin and ZO-1 and upregulation of the mesenchymal markers N-cadherin, vimentin, and Snail. Further investigation revealed that calpain-2 was involved in baicalein suppression of FN-induced EMT. Baicalein significantly decreased FN-enhanced calpain-2 expression and activation by suppressing its plasma membrane localization, substrate cleavage, and degradation of its endogenous inhibitor calpastatin. Overexpression of calpain-2 in MCF-10A cells by gene transfection partially blocked the inhibitory effect of baicalein on FN-induced EMT changes. In addition, baicalein inhibited calpain-2 by decreasing FN-increased intracellular calcium ion levels and extracellular signal-regulated protein kinases activation. Baicalein significantly decreased tumor onset, growth, and pulmonary metastasis in a spontaneous breast cancer MMTV-PyMT mouse model. Baicalein also reduced the expression of FN, calpain-2, and vimentin, but increased E-cadherin expression in MMTV-PyMT mouse tumors. Overall, these results revealed that baicalein markedly inhibited FN-induced EMT by inhibiting calpain-2, thus providing novel insights into the pharmacological action and mechanism of baicalein. Baicalein may therefore possess therapeutic potential for the treatment of breast cancer though interfering with extracellular matrix–cancer cell interactions.</description><subject>14/19</subject><subject>631/154/436/2388</subject><subject>64</subject><subject>64/60</subject><subject>692/308/153</subject><subject>96/109</subject><subject>96/31</subject><subject>Actin</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Butadienes - pharmacology</subject><subject>Cadherins - metabolism</subject><subject>Calcium (extracellular)</subject><subject>Calcium (intracellular)</subject><subject>Calcium - metabolism</subject><subject>Calpain</subject><subject>Calpain - metabolism</subject><subject>Calpastatin</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell interactions</subject><subject>Cell Line, Tumor</subject><subject>E-cadherin</subject><subject>Epithelial cells</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Extracellular matrix</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>Fibronectin</subject><subject>Fibronectins - metabolism</subject><subject>Flavanones - pharmacology</subject><subject>Flavanones - therapeutic use</subject><subject>Humans</subject><subject>Immunology</subject><subject>Kaplan-Meier Estimate</subject><subject>Life Sciences</subject><subject>Localization</subject><subject>Matrix protein</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>N-Cadherin</subject><subject>Nitriles - pharmacology</subject><subject>Protein kinase</subject><subject>Transfection</subject><subject>Transgenic mice</subject><subject>Tumorigenesis</subject><subject>Up-regulation</subject><subject>Up-Regulation - drug effects</subject><subject>Vimentin</subject><subject>Zonula occludens-1 protein</subject><subject>Zonula Occludens-1 Protein - metabolism</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1Uc1KHTEUDqWiYn0ANyXQ9dicZG5mZiNYqa0gdFPX4Uxy5t7I3Mw0mRHurn2GvqFPYuyotYsGQn7O9wcfYycgTkGo-mMqoYSmEHnDqpJF9YYdSlFCUdZ18_bV_YAdp3Qr8lJKyJXeZwcK8ks3-pD9-oTeYk8-cB82vvVT4p1v4xDITj4UPrjZkuM0-mlDvcf-_ufvLSUKdrPbYs-niCH5yQ-BtzvuyEbC5MOaY-bf4Z8BBsfnMdJ67pePoePZdMRsIN-xvQ77RMdP5xG7ufz8_eJrcf3ty9XF-XVhV0pPhQQB5EBSK6wjV5FuQddakWoBtZO6bOpaUyewpso2rlOEqqyEbICkwEYdsbNFd5zbLTlLIUfvzRj9FuPODOjNv5PgN2Y93BldVnIlyizw4UkgDj9mSpO5HeYYcmYjJYCSQuo6o2BB2TikFKl7cQBhHoszS3EmF2ceizNV5rx_He2F8VxTBsgFkPIorCn-tf6_6gMh_6hn</recordid><startdate>20190418</startdate><enddate>20190418</enddate><creator>Chen, Yan</creator><creator>Chen, Lin</creator><creator>Hong, Duanyang</creator><creator>Chen, Zongyue</creator><creator>Zhang, Jingyu</creator><creator>Fu, Lingyun</creator><creator>Pan, Di</creator><creator>Zhang, Yanyan</creator><creator>Xu, Yini</creator><creator>Gan, Shiquan</creator><creator>Xiao, Chaoda</creator><creator>Tao, Ling</creator><creator>Shen, Xiangchun</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</scope><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>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20190418</creationdate><title>Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2</title><author>Chen, Yan ; Chen, Lin ; Hong, Duanyang ; Chen, Zongyue ; Zhang, Jingyu ; Fu, Lingyun ; Pan, Di ; Zhang, Yanyan ; Xu, Yini ; Gan, Shiquan ; Xiao, Chaoda ; Tao, Ling ; Shen, Xiangchun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-2101ed12eb0cded7e6b16863e3b1a6d2649886ef0a8e7c9df3ea3470291e20a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>14/19</topic><topic>631/154/436/2388</topic><topic>64</topic><topic>64/60</topic><topic>692/308/153</topic><topic>96/109</topic><topic>96/31</topic><topic>Actin</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Butadienes - pharmacology</topic><topic>Cadherins - metabolism</topic><topic>Calcium (extracellular)</topic><topic>Calcium (intracellular)</topic><topic>Calcium - metabolism</topic><topic>Calpain</topic><topic>Calpain - metabolism</topic><topic>Calpastatin</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell interactions</topic><topic>Cell Line, Tumor</topic><topic>E-cadherin</topic><topic>Epithelial cells</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Extracellular matrix</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>Fibronectin</topic><topic>Fibronectins - metabolism</topic><topic>Flavanones - pharmacology</topic><topic>Flavanones - therapeutic use</topic><topic>Humans</topic><topic>Immunology</topic><topic>Kaplan-Meier Estimate</topic><topic>Life Sciences</topic><topic>Localization</topic><topic>Matrix protein</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>N-Cadherin</topic><topic>Nitriles - pharmacology</topic><topic>Protein kinase</topic><topic>Transfection</topic><topic>Transgenic mice</topic><topic>Tumorigenesis</topic><topic>Up-regulation</topic><topic>Up-Regulation - drug effects</topic><topic>Vimentin</topic><topic>Zonula occludens-1 protein</topic><topic>Zonula Occludens-1 Protein - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yan</creatorcontrib><creatorcontrib>Chen, Lin</creatorcontrib><creatorcontrib>Hong, Duanyang</creatorcontrib><creatorcontrib>Chen, Zongyue</creatorcontrib><creatorcontrib>Zhang, Jingyu</creatorcontrib><creatorcontrib>Fu, Lingyun</creatorcontrib><creatorcontrib>Pan, Di</creatorcontrib><creatorcontrib>Zhang, Yanyan</creatorcontrib><creatorcontrib>Xu, Yini</creatorcontrib><creatorcontrib>Gan, Shiquan</creatorcontrib><creatorcontrib>Xiao, Chaoda</creatorcontrib><creatorcontrib>Tao, Ling</creatorcontrib><creatorcontrib>Shen, Xiangchun</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</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>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yan</au><au>Chen, Lin</au><au>Hong, Duanyang</au><au>Chen, Zongyue</au><au>Zhang, Jingyu</au><au>Fu, Lingyun</au><au>Pan, Di</au><au>Zhang, Yanyan</au><au>Xu, Yini</au><au>Gan, Shiquan</au><au>Xiao, Chaoda</au><au>Tao, Ling</au><au>Shen, Xiangchun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2019-04-18</date><risdate>2019</risdate><volume>10</volume><issue>5</issue><spage>341</spage><pages>341-</pages><artnum>341</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>The extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial–mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced migration, invasion, and F-actin remodeling. Baicalein also suppressed FN-induced downregulation of the epithelial markers E-cadherin and ZO-1 and upregulation of the mesenchymal markers N-cadherin, vimentin, and Snail. Further investigation revealed that calpain-2 was involved in baicalein suppression of FN-induced EMT. Baicalein significantly decreased FN-enhanced calpain-2 expression and activation by suppressing its plasma membrane localization, substrate cleavage, and degradation of its endogenous inhibitor calpastatin. Overexpression of calpain-2 in MCF-10A cells by gene transfection partially blocked the inhibitory effect of baicalein on FN-induced EMT changes. In addition, baicalein inhibited calpain-2 by decreasing FN-increased intracellular calcium ion levels and extracellular signal-regulated protein kinases activation. Baicalein significantly decreased tumor onset, growth, and pulmonary metastasis in a spontaneous breast cancer MMTV-PyMT mouse model. Baicalein also reduced the expression of FN, calpain-2, and vimentin, but increased E-cadherin expression in MMTV-PyMT mouse tumors. Overall, these results revealed that baicalein markedly inhibited FN-induced EMT by inhibiting calpain-2, thus providing novel insights into the pharmacological action and mechanism of baicalein. Baicalein may therefore possess therapeutic potential for the treatment of breast cancer though interfering with extracellular matrix–cancer cell interactions.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31000696</pmid><doi>10.1038/s41419-019-1572-7</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-4889 |
| ispartof | Cell death & disease, 2019-04, Vol.10 (5), p.341, Article 341 |
| issn | 2041-4889 2041-4889 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6472504 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Springer Nature OA Free Journals; Nature Free; PubMed Central |
| subjects | 14/19 631/154/436/2388 64 64/60 692/308/153 96/109 96/31 Actin Animals Antibodies Biochemistry Biomedical and Life Sciences Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - mortality Breast Neoplasms - pathology Butadienes - pharmacology Cadherins - metabolism Calcium (extracellular) Calcium (intracellular) Calcium - metabolism Calpain Calpain - metabolism Calpastatin Cell Biology Cell Culture Cell interactions Cell Line, Tumor E-cadherin Epithelial cells Epithelial-Mesenchymal Transition - drug effects Extracellular matrix Extracellular Signal-Regulated MAP Kinases - metabolism Female Fibronectin Fibronectins - metabolism Flavanones - pharmacology Flavanones - therapeutic use Humans Immunology Kaplan-Meier Estimate Life Sciences Localization Matrix protein Mesenchyme Metastases Mice Mice, Transgenic N-Cadherin Nitriles - pharmacology Protein kinase Transfection Transgenic mice Tumorigenesis Up-regulation Up-Regulation - drug effects Vimentin Zonula occludens-1 protein Zonula Occludens-1 Protein - metabolism |
| title | Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T05%3A10%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Baicalein%20inhibits%20fibronectin-induced%20epithelial%E2%80%93mesenchymal%20transition%20by%20decreasing%20activation%20and%20upregulation%20of%20calpain-2&rft.jtitle=Cell%20death%20&%20disease&rft.au=Chen,%20Yan&rft.date=2019-04-18&rft.volume=10&rft.issue=5&rft.spage=341&rft.pages=341-&rft.artnum=341&rft.issn=2041-4889&rft.eissn=2041-4889&rft_id=info:doi/10.1038/s41419-019-1572-7&rft_dat=%3Cproquest_pubme%3E2211320268%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2211320268&rft_id=info:pmid/31000696&rfr_iscdi=true |