Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression
Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration an...
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| Veröffentlicht in: | Cancers 2021-03, Vol.13 (5), p.1174 |
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| creator | Hsin, Min-Chieh Hsieh, Yi-Hsien Hsiao, Yi-Hsuan Chen, Pei-Ni Wang, Po-Hui Yang, Shun-Fa |
| description | Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human cervical cancer patients with CAIX
/PFKFB4
expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy. |
| doi_str_mv | 10.3390/cancers13051174 |
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/PFKFB4
expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13051174</identifier><identifier>PMID: 33803236</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>6-Phosphofructo-2-kinase ; Antibodies ; Breast cancer ; Cell adhesion & migration ; Cell cycle ; Cell growth ; Cell migration ; Cervical cancer ; Cloning ; Human papillomavirus ; Hypoxia ; Kinases ; Lung cancer ; Lymph nodes ; Mesenchyme ; Metabolism ; Metastases ; Metastasis ; Molecular modelling ; Phosphorylation ; Sequence analysis</subject><ispartof>Cancers, 2021-03, Vol.13 (5), p.1174</ispartof><rights>2021. 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>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-dec8acf70ae7285cffa3b864a29f059d11941b3fc093738df55ebb0f976329f83</citedby><cites>FETCH-LOGICAL-c421t-dec8acf70ae7285cffa3b864a29f059d11941b3fc093738df55ebb0f976329f83</cites><orcidid>0000-0003-4942-1888 ; 0000-0002-0365-7927</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/PMC7967120/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967120/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33803236$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsin, Min-Chieh</creatorcontrib><creatorcontrib>Hsieh, Yi-Hsien</creatorcontrib><creatorcontrib>Hsiao, Yi-Hsuan</creatorcontrib><creatorcontrib>Chen, Pei-Ni</creatorcontrib><creatorcontrib>Wang, Po-Hui</creatorcontrib><creatorcontrib>Yang, Shun-Fa</creatorcontrib><title>Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human cervical cancer patients with CAIX
/PFKFB4
expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy.</description><subject>6-Phosphofructo-2-kinase</subject><subject>Antibodies</subject><subject>Breast cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell migration</subject><subject>Cervical cancer</subject><subject>Cloning</subject><subject>Human papillomavirus</subject><subject>Hypoxia</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lymph nodes</subject><subject>Mesenchyme</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Molecular modelling</subject><subject>Phosphorylation</subject><subject>Sequence analysis</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><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>eNpdkcFLBCEUxiWKiurcLYQuXbZ0dMbxEmxDW0tFEQXdxHF0c5nRTWei_e-z2qLy8pT383t-fgDsY3RMCEcnSjqlQ8QE5Rgzuga2M8SyUVFwuv5rvwX2YpyjtAjBrGCbYIuQEpGMFNugrmSovbMKjt3zsgkyajh9gnfBd77XEV4OnXSw0uHVKtnC6nNkOrctvPG9bW2_hPUS3uvZ0Mreuhm8m1xNzig8f1sEHaP1bhdsGNlGvbeqO-Bxcv5QXY6uby-m1fh6pGiG-1GjVSmVYUhqlpW5MkaSuiyozLhBOW8w5hTXxCjECSNlY_Jc1zUynBUkISXZAadfuouh7nSjtOuDbMUi2E6GpfDSir8dZ5_FzL8KxguGM5QEjlYCwb8MOvais1Elq9JpP0SR5ajMS0xzmtDDf-jcD8Elex8UTh9dUJ6oky9KBR9j0ObnMRiJjwjFvwjTjYPfHn7478DIO1wImL4</recordid><startdate>20210309</startdate><enddate>20210309</enddate><creator>Hsin, Min-Chieh</creator><creator>Hsieh, Yi-Hsien</creator><creator>Hsiao, Yi-Hsuan</creator><creator>Chen, Pei-Ni</creator><creator>Wang, Po-Hui</creator><creator>Yang, Shun-Fa</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4942-1888</orcidid><orcidid>https://orcid.org/0000-0002-0365-7927</orcidid></search><sort><creationdate>20210309</creationdate><title>Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression</title><author>Hsin, Min-Chieh ; Hsieh, Yi-Hsien ; Hsiao, Yi-Hsuan ; Chen, Pei-Ni ; Wang, Po-Hui ; Yang, Shun-Fa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-dec8acf70ae7285cffa3b864a29f059d11941b3fc093738df55ebb0f976329f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>6-Phosphofructo-2-kinase</topic><topic>Antibodies</topic><topic>Breast cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell migration</topic><topic>Cervical cancer</topic><topic>Cloning</topic><topic>Human papillomavirus</topic><topic>Hypoxia</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Lymph nodes</topic><topic>Mesenchyme</topic><topic>Metabolism</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Molecular modelling</topic><topic>Phosphorylation</topic><topic>Sequence analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsin, Min-Chieh</creatorcontrib><creatorcontrib>Hsieh, Yi-Hsien</creatorcontrib><creatorcontrib>Hsiao, Yi-Hsuan</creatorcontrib><creatorcontrib>Chen, Pei-Ni</creatorcontrib><creatorcontrib>Wang, Po-Hui</creatorcontrib><creatorcontrib>Yang, Shun-Fa</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>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>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsin, Min-Chieh</au><au>Hsieh, Yi-Hsien</au><au>Hsiao, Yi-Hsuan</au><au>Chen, Pei-Ni</au><au>Wang, Po-Hui</au><au>Yang, Shun-Fa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2021-03-09</date><risdate>2021</risdate><volume>13</volume><issue>5</issue><spage>1174</spage><pages>1174-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human cervical cancer patients with CAIX
/PFKFB4
expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33803236</pmid><doi>10.3390/cancers13051174</doi><orcidid>https://orcid.org/0000-0003-4942-1888</orcidid><orcidid>https://orcid.org/0000-0002-0365-7927</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 6-Phosphofructo-2-kinase Antibodies Breast cancer Cell adhesion & migration Cell cycle Cell growth Cell migration Cervical cancer Cloning Human papillomavirus Hypoxia Kinases Lung cancer Lymph nodes Mesenchyme Metabolism Metastases Metastasis Molecular modelling Phosphorylation Sequence analysis |
| title | Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression |
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