HIF‐1α is necessary for activation and tumour‐promotion effect of cancer‐associated fibroblasts in lung cancer
Cancer‐associated fibroblasts (CAFs) activation is crucial for the establishment of a tumour promoting microenvironment, but our understanding of CAFs activation is still limited. In this study, we found that hypoxia‐inducible factor‐1α (HIF‐1α) was highly expressed in CAFs of human lung cancer tiss...
Gespeichert in:
| Veröffentlicht in: | Journal of cellular and molecular medicine 2021-06, Vol.25 (12), p.5457-5469 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5469 |
|---|---|
| container_issue | 12 |
| container_start_page | 5457 |
| container_title | Journal of cellular and molecular medicine |
| container_volume | 25 |
| creator | Zhang, Yana Bian, Yangyang Wang, Yuan Wang, Yuanyuan Duan, Xixi Han, Yuning Zhang, Lijing Wang, Fei Gu, Zhuoyu Qin, Zhihai |
| description | Cancer‐associated fibroblasts (CAFs) activation is crucial for the establishment of a tumour promoting microenvironment, but our understanding of CAFs activation is still limited. In this study, we found that hypoxia‐inducible factor‐1α (HIF‐1α) was highly expressed in CAFs of human lung cancer tissues and mouse spontaneous lung tumour. Accordingly, enhancing the expression of HIF‐1α in fibroblasts via hypoxia induced the conversion of normal fibroblasts into CAFs. HIF‐1α‐specific inhibitor or HIF‐1α knockout (KO) significantly attenuated CAFs activation, which was manifested by the decreased expression of COL1A2 and α‐SMA. In vivo, during tumour formation, the expression of Ki‐67 and proliferating cell nuclear antigen (PCNA) in the tumour tissue with HIF‐1α KO fibroblasts was significantly lower than that of normal fibroblasts. Moreover, HIF‐1α in fibroblasts could activate the NF‐κB signalling pathway and enhance a subsequent secretion of CCL5, thus promoting the tumour growth. In conclusion, our results suggest that HIF‐1α is essential for the activation and tumour‐promotion function of CAFs in lung cancer (LC). And targeting HIF‐1α expression on CAFs may be a promising strategy for LC therapy. |
| doi_str_mv | 10.1111/jcmm.16556 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8184678</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2522187300</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4486-d6ee5103e5e02e14dbdd9d16b629330a7a8aa242c62623f41f6777b02fd1d7933</originalsourceid><addsrcrecordid>eNp9kU1uFDEQhS1ERMLAhgMgS2wQ0oT2T7vdG6RoREiiRGxgbbntcvCo2x7s7qDsOEKukovkEDkJ7swQAQu8scv16elVPYRekeqQlPN-bYbhkIi6Fk_QAaklXfKW8ae7N5FM7qPnOa-rignC2mdon7GWs1IeoOnk9Pj-5w25u8U-4wAGctbpGruYsDajv9KjjwHrYPE4DXFKBd6kOMSHb3AOzIijw0YHA3NT5xyN1yNY7HyXYtfrPGbsA-6ncLnjXqA9p_sML3f3An09_vhldbI8__zpdHV0vjScS7G0AqAmFYMaKgqE287a1hLRCdoyVulGS60pp0ZQQZnjxImmabqKOktsU5AF-rDV3UzdANZAGJPu1Sb5oQypovbq707w39RlvFKSSC4aWQTe7gRS_D5BHtXgs4G-1wHilBWtKSWymXe5QG_-QddlXaGMVyjWyJIFmR2921ImxZwTuEczpFJzmmpOUz2kWeDXf9p_RH_HVwCyBX74Hq7_I6XOVhcXW9Ff7Nmvpw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2537858213</pqid></control><display><type>article</type><title>HIF‐1α is necessary for activation and tumour‐promotion effect of cancer‐associated fibroblasts in lung cancer</title><source>Wiley Journals</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley-Blackwell Open Access Titles</source><source>PubMed Central</source><creator>Zhang, Yana ; Bian, Yangyang ; Wang, Yuan ; Wang, Yuanyuan ; Duan, Xixi ; Han, Yuning ; Zhang, Lijing ; Wang, Fei ; Gu, Zhuoyu ; Qin, Zhihai</creator><creatorcontrib>Zhang, Yana ; Bian, Yangyang ; Wang, Yuan ; Wang, Yuanyuan ; Duan, Xixi ; Han, Yuning ; Zhang, Lijing ; Wang, Fei ; Gu, Zhuoyu ; Qin, Zhihai</creatorcontrib><description>Cancer‐associated fibroblasts (CAFs) activation is crucial for the establishment of a tumour promoting microenvironment, but our understanding of CAFs activation is still limited. In this study, we found that hypoxia‐inducible factor‐1α (HIF‐1α) was highly expressed in CAFs of human lung cancer tissues and mouse spontaneous lung tumour. Accordingly, enhancing the expression of HIF‐1α in fibroblasts via hypoxia induced the conversion of normal fibroblasts into CAFs. HIF‐1α‐specific inhibitor or HIF‐1α knockout (KO) significantly attenuated CAFs activation, which was manifested by the decreased expression of COL1A2 and α‐SMA. In vivo, during tumour formation, the expression of Ki‐67 and proliferating cell nuclear antigen (PCNA) in the tumour tissue with HIF‐1α KO fibroblasts was significantly lower than that of normal fibroblasts. Moreover, HIF‐1α in fibroblasts could activate the NF‐κB signalling pathway and enhance a subsequent secretion of CCL5, thus promoting the tumour growth. In conclusion, our results suggest that HIF‐1α is essential for the activation and tumour‐promotion function of CAFs in lung cancer (LC). And targeting HIF‐1α expression on CAFs may be a promising strategy for LC therapy.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.16556</identifier><identifier>PMID: 33943003</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Antibodies ; Breast cancer ; CAFs ; CCL5 ; CRISPR ; Fibroblasts ; Growth factors ; HIF‐1α ; Hypoxia ; Lung cancer ; Microenvironments ; Original ; Plasmids ; Proliferating cell nuclear antigen ; Proteins ; Signal transduction ; Tumors</subject><ispartof>Journal of cellular and molecular medicine, 2021-06, Vol.25 (12), p.5457-5469</ispartof><rights>2021 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2021. 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-c4486-d6ee5103e5e02e14dbdd9d16b629330a7a8aa242c62623f41f6777b02fd1d7933</citedby><cites>FETCH-LOGICAL-c4486-d6ee5103e5e02e14dbdd9d16b629330a7a8aa242c62623f41f6777b02fd1d7933</cites><orcidid>0000-0001-9793-7964</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/PMC8184678/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184678/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33943003$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yana</creatorcontrib><creatorcontrib>Bian, Yangyang</creatorcontrib><creatorcontrib>Wang, Yuan</creatorcontrib><creatorcontrib>Wang, Yuanyuan</creatorcontrib><creatorcontrib>Duan, Xixi</creatorcontrib><creatorcontrib>Han, Yuning</creatorcontrib><creatorcontrib>Zhang, Lijing</creatorcontrib><creatorcontrib>Wang, Fei</creatorcontrib><creatorcontrib>Gu, Zhuoyu</creatorcontrib><creatorcontrib>Qin, Zhihai</creatorcontrib><title>HIF‐1α is necessary for activation and tumour‐promotion effect of cancer‐associated fibroblasts in lung cancer</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Cancer‐associated fibroblasts (CAFs) activation is crucial for the establishment of a tumour promoting microenvironment, but our understanding of CAFs activation is still limited. In this study, we found that hypoxia‐inducible factor‐1α (HIF‐1α) was highly expressed in CAFs of human lung cancer tissues and mouse spontaneous lung tumour. Accordingly, enhancing the expression of HIF‐1α in fibroblasts via hypoxia induced the conversion of normal fibroblasts into CAFs. HIF‐1α‐specific inhibitor or HIF‐1α knockout (KO) significantly attenuated CAFs activation, which was manifested by the decreased expression of COL1A2 and α‐SMA. In vivo, during tumour formation, the expression of Ki‐67 and proliferating cell nuclear antigen (PCNA) in the tumour tissue with HIF‐1α KO fibroblasts was significantly lower than that of normal fibroblasts. Moreover, HIF‐1α in fibroblasts could activate the NF‐κB signalling pathway and enhance a subsequent secretion of CCL5, thus promoting the tumour growth. In conclusion, our results suggest that HIF‐1α is essential for the activation and tumour‐promotion function of CAFs in lung cancer (LC). And targeting HIF‐1α expression on CAFs may be a promising strategy for LC therapy.</description><subject>Antibodies</subject><subject>Breast cancer</subject><subject>CAFs</subject><subject>CCL5</subject><subject>CRISPR</subject><subject>Fibroblasts</subject><subject>Growth factors</subject><subject>HIF‐1α</subject><subject>Hypoxia</subject><subject>Lung cancer</subject><subject>Microenvironments</subject><subject>Original</subject><subject>Plasmids</subject><subject>Proliferating cell nuclear antigen</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Tumors</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1uFDEQhS1ERMLAhgMgS2wQ0oT2T7vdG6RoREiiRGxgbbntcvCo2x7s7qDsOEKukovkEDkJ7swQAQu8scv16elVPYRekeqQlPN-bYbhkIi6Fk_QAaklXfKW8ae7N5FM7qPnOa-rignC2mdon7GWs1IeoOnk9Pj-5w25u8U-4wAGctbpGruYsDajv9KjjwHrYPE4DXFKBd6kOMSHb3AOzIijw0YHA3NT5xyN1yNY7HyXYtfrPGbsA-6ncLnjXqA9p_sML3f3An09_vhldbI8__zpdHV0vjScS7G0AqAmFYMaKgqE287a1hLRCdoyVulGS60pp0ZQQZnjxImmabqKOktsU5AF-rDV3UzdANZAGJPu1Sb5oQypovbq707w39RlvFKSSC4aWQTe7gRS_D5BHtXgs4G-1wHilBWtKSWymXe5QG_-QddlXaGMVyjWyJIFmR2921ImxZwTuEczpFJzmmpOUz2kWeDXf9p_RH_HVwCyBX74Hq7_I6XOVhcXW9Ff7Nmvpw</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Zhang, Yana</creator><creator>Bian, Yangyang</creator><creator>Wang, Yuan</creator><creator>Wang, Yuanyuan</creator><creator>Duan, Xixi</creator><creator>Han, Yuning</creator><creator>Zhang, Lijing</creator><creator>Wang, Fei</creator><creator>Gu, Zhuoyu</creator><creator>Qin, Zhihai</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9793-7964</orcidid></search><sort><creationdate>202106</creationdate><title>HIF‐1α is necessary for activation and tumour‐promotion effect of cancer‐associated fibroblasts in lung cancer</title><author>Zhang, Yana ; Bian, Yangyang ; Wang, Yuan ; Wang, Yuanyuan ; Duan, Xixi ; Han, Yuning ; Zhang, Lijing ; Wang, Fei ; Gu, Zhuoyu ; Qin, Zhihai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4486-d6ee5103e5e02e14dbdd9d16b629330a7a8aa242c62623f41f6777b02fd1d7933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Breast cancer</topic><topic>CAFs</topic><topic>CCL5</topic><topic>CRISPR</topic><topic>Fibroblasts</topic><topic>Growth factors</topic><topic>HIF‐1α</topic><topic>Hypoxia</topic><topic>Lung cancer</topic><topic>Microenvironments</topic><topic>Original</topic><topic>Plasmids</topic><topic>Proliferating cell nuclear antigen</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yana</creatorcontrib><creatorcontrib>Bian, Yangyang</creatorcontrib><creatorcontrib>Wang, Yuan</creatorcontrib><creatorcontrib>Wang, Yuanyuan</creatorcontrib><creatorcontrib>Duan, Xixi</creatorcontrib><creatorcontrib>Han, Yuning</creatorcontrib><creatorcontrib>Zhang, Lijing</creatorcontrib><creatorcontrib>Wang, Fei</creatorcontrib><creatorcontrib>Gu, Zhuoyu</creatorcontrib><creatorcontrib>Qin, Zhihai</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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>Engineering Research Database</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>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yana</au><au>Bian, Yangyang</au><au>Wang, Yuan</au><au>Wang, Yuanyuan</au><au>Duan, Xixi</au><au>Han, Yuning</au><au>Zhang, Lijing</au><au>Wang, Fei</au><au>Gu, Zhuoyu</au><au>Qin, Zhihai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HIF‐1α is necessary for activation and tumour‐promotion effect of cancer‐associated fibroblasts in lung cancer</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2021-06</date><risdate>2021</risdate><volume>25</volume><issue>12</issue><spage>5457</spage><epage>5469</epage><pages>5457-5469</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Cancer‐associated fibroblasts (CAFs) activation is crucial for the establishment of a tumour promoting microenvironment, but our understanding of CAFs activation is still limited. In this study, we found that hypoxia‐inducible factor‐1α (HIF‐1α) was highly expressed in CAFs of human lung cancer tissues and mouse spontaneous lung tumour. Accordingly, enhancing the expression of HIF‐1α in fibroblasts via hypoxia induced the conversion of normal fibroblasts into CAFs. HIF‐1α‐specific inhibitor or HIF‐1α knockout (KO) significantly attenuated CAFs activation, which was manifested by the decreased expression of COL1A2 and α‐SMA. In vivo, during tumour formation, the expression of Ki‐67 and proliferating cell nuclear antigen (PCNA) in the tumour tissue with HIF‐1α KO fibroblasts was significantly lower than that of normal fibroblasts. Moreover, HIF‐1α in fibroblasts could activate the NF‐κB signalling pathway and enhance a subsequent secretion of CCL5, thus promoting the tumour growth. In conclusion, our results suggest that HIF‐1α is essential for the activation and tumour‐promotion function of CAFs in lung cancer (LC). And targeting HIF‐1α expression on CAFs may be a promising strategy for LC therapy.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>33943003</pmid><doi>10.1111/jcmm.16556</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-9793-7964</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1582-1838 |
| ispartof | Journal of cellular and molecular medicine, 2021-06, Vol.25 (12), p.5457-5469 |
| issn | 1582-1838 1582-4934 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8184678 |
| source | Wiley Journals; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley-Blackwell Open Access Titles; PubMed Central |
| subjects | Antibodies Breast cancer CAFs CCL5 CRISPR Fibroblasts Growth factors HIF‐1α Hypoxia Lung cancer Microenvironments Original Plasmids Proliferating cell nuclear antigen Proteins Signal transduction Tumors |
| title | HIF‐1α is necessary for activation and tumour‐promotion effect of cancer‐associated fibroblasts in lung cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T21%3A23%3A42IST&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=HIF%E2%80%901%CE%B1%20is%20necessary%20for%20activation%20and%20tumour%E2%80%90promotion%20effect%20of%20cancer%E2%80%90associated%20fibroblasts%20in%20lung%20cancer&rft.jtitle=Journal%20of%20cellular%20and%20molecular%20medicine&rft.au=Zhang,%20Yana&rft.date=2021-06&rft.volume=25&rft.issue=12&rft.spage=5457&rft.epage=5469&rft.pages=5457-5469&rft.issn=1582-1838&rft.eissn=1582-4934&rft_id=info:doi/10.1111/jcmm.16556&rft_dat=%3Cproquest_pubme%3E2522187300%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=2537858213&rft_id=info:pmid/33943003&rfr_iscdi=true |