CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation
Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y‐box as a cis‐acting element. As a parallel analysis of database records for 149 n...
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| Veröffentlicht in: | Cancer science 2021-07, Vol.112 (7), p.2770-2780 |
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| creator | Shi, Hanxiao Niimi, Atsuko Takeuchi, Toshiyuki Shiogama, Kazuya Mizutani, Yasuyoshi Kajino, Taisuke Inada, Kenichi Hase, Tetsunari Hatta, Takahiro Shibata, Hirofumi Fukui, Takayuki Chen‐Yoshikawa, Toyofumi Fengshi Nagano, Kazuki Murate, Takashi Kawamoto, Yoshiyuki Tomida, Shuta Takahashi, Takashi Suzuki, Motoshi |
| description | Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y‐box as a cis‐acting element. As a parallel analysis of database records for 149 non–small‐cell lung cancer (NSCLC) cancer patients, we screened for trans‐acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer‐binding protein γ (CEBPγ) or Y‐box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide‐dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y‐box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.
Schematic illustration showing CEBPγ functions for cancer cell migration. |
| doi_str_mv | 10.1111/cas.14928 |
| format | Article |
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Schematic illustration showing CEBPγ functions for cancer cell migration.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.14928</identifier><identifier>PMID: 33934437</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adenocarcinoma ; Antibodies ; B cells ; Binding sites ; Cancer therapies ; CEBPγ ; Cell adhesion & migration ; Cell migration ; Ceramide ; CERS6 ; DNA binding proteins ; Enzymes ; Ethylenediaminetetraacetic acid ; Experiments ; Gene expression ; Invasiveness ; Kinases ; Lamellipodia ; Leukemia ; Lipids ; Luciferase ; Lung cancer ; Lung cancer, Non-small cell ; Medical prognosis ; Metabolism ; Metastases ; Metastasis ; Mutagenesis ; Non-small cell lung carcinoma ; Original ; Pathogenesis ; Protein binding ; Proteins ; Pseudopodia ; Transcription factors ; YBX1</subject><ispartof>Cancer science, 2021-07, Vol.112 (7), p.2770-2780</ispartof><rights>2021 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>COPYRIGHT 2021 John Wiley & Sons, Inc.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by-nc-nd/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-c5628-3e3237e31fb8356d8f6fa9181e520775c88293feaed1c3e964809b3d4448bc583</citedby><cites>FETCH-LOGICAL-c5628-3e3237e31fb8356d8f6fa9181e520775c88293feaed1c3e964809b3d4448bc583</cites><orcidid>0000-0003-0682-5006 ; 0000-0003-0615-7001</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/PMC8253294/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253294/$$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/33934437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Hanxiao</creatorcontrib><creatorcontrib>Niimi, Atsuko</creatorcontrib><creatorcontrib>Takeuchi, Toshiyuki</creatorcontrib><creatorcontrib>Shiogama, Kazuya</creatorcontrib><creatorcontrib>Mizutani, Yasuyoshi</creatorcontrib><creatorcontrib>Kajino, Taisuke</creatorcontrib><creatorcontrib>Inada, Kenichi</creatorcontrib><creatorcontrib>Hase, Tetsunari</creatorcontrib><creatorcontrib>Hatta, Takahiro</creatorcontrib><creatorcontrib>Shibata, Hirofumi</creatorcontrib><creatorcontrib>Fukui, Takayuki</creatorcontrib><creatorcontrib>Chen‐Yoshikawa, Toyofumi Fengshi</creatorcontrib><creatorcontrib>Nagano, Kazuki</creatorcontrib><creatorcontrib>Murate, Takashi</creatorcontrib><creatorcontrib>Kawamoto, Yoshiyuki</creatorcontrib><creatorcontrib>Tomida, Shuta</creatorcontrib><creatorcontrib>Takahashi, Takashi</creatorcontrib><creatorcontrib>Suzuki, Motoshi</creatorcontrib><title>CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y‐box as a cis‐acting element. As a parallel analysis of database records for 149 non–small‐cell lung cancer (NSCLC) cancer patients, we screened for trans‐acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer‐binding protein γ (CEBPγ) or Y‐box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide‐dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y‐box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.
Schematic illustration showing CEBPγ functions for cancer cell migration.</description><subject>Adenocarcinoma</subject><subject>Antibodies</subject><subject>B cells</subject><subject>Binding sites</subject><subject>Cancer therapies</subject><subject>CEBPγ</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>Ceramide</subject><subject>CERS6</subject><subject>DNA binding proteins</subject><subject>Enzymes</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Experiments</subject><subject>Gene expression</subject><subject>Invasiveness</subject><subject>Kinases</subject><subject>Lamellipodia</subject><subject>Leukemia</subject><subject>Lipids</subject><subject>Luciferase</subject><subject>Lung cancer</subject><subject>Lung cancer, Non-small cell</subject><subject>Medical prognosis</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mutagenesis</subject><subject>Non-small cell lung carcinoma</subject><subject>Original</subject><subject>Pathogenesis</subject><subject>Protein binding</subject><subject>Proteins</subject><subject>Pseudopodia</subject><subject>Transcription factors</subject><subject>YBX1</subject><issn>1347-9032</issn><issn>1349-7006</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>eNqFks9u1DAQxiMEoqVw4AVQJC5wyNb_EtsXpCVaWqRKIApXLK8zzrpK4q2dgPpcvAfPhHfTlhaBsA-2_P3mG89osuw5Rguc1rHRcYGZJOJBdogpkwVHqHq4v_NCIkoOsicxXiBEKybZ4-yAUkkZo_ww-1qv3n78-SO32rjOjXqEmHe6h65zW984nVsfej06P-R6aHKjBwMhN0nPe9eGWRk3wU_tJq9Xn86rfNoGaKduLz3NHlndRXh2fR5lX96tPtenxdmHk_f18qwwZUVEQYESyoFiuxa0rBphK6slFhhKgjgvjRBEUgsaGmwoyIoJJNe0YYyJtSkFPcrezL7bad1DY2AYg-7UNrhehyvltVP3lcFtVOu_KUFKSiRLBq-uDYK_nCCOqndxV6YewE9RkZKkDotK8oS-_AO98FMYUnmJkoIiUYr_UIyXlSQM_6Za3YFyg_Xpd2aXWi05RpxRzHfVLf5Cpd1A74wfwLr0fi_g9Rxggo8xgL3tBEZqNzIqjYzaj0xiX9xt3S15MyMJOJ6B7ynL1b-dVL08ny1_AUXiyTQ</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Shi, 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expression</topic><topic>Invasiveness</topic><topic>Kinases</topic><topic>Lamellipodia</topic><topic>Leukemia</topic><topic>Lipids</topic><topic>Luciferase</topic><topic>Lung cancer</topic><topic>Lung cancer, Non-small cell</topic><topic>Medical prognosis</topic><topic>Metabolism</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mutagenesis</topic><topic>Non-small cell lung carcinoma</topic><topic>Original</topic><topic>Pathogenesis</topic><topic>Protein binding</topic><topic>Proteins</topic><topic>Pseudopodia</topic><topic>Transcription factors</topic><topic>YBX1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Hanxiao</creatorcontrib><creatorcontrib>Niimi, Atsuko</creatorcontrib><creatorcontrib>Takeuchi, Toshiyuki</creatorcontrib><creatorcontrib>Shiogama, Kazuya</creatorcontrib><creatorcontrib>Mizutani, Yasuyoshi</creatorcontrib><creatorcontrib>Kajino, Taisuke</creatorcontrib><creatorcontrib>Inada, 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Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Hanxiao</au><au>Niimi, Atsuko</au><au>Takeuchi, Toshiyuki</au><au>Shiogama, Kazuya</au><au>Mizutani, Yasuyoshi</au><au>Kajino, Taisuke</au><au>Inada, Kenichi</au><au>Hase, Tetsunari</au><au>Hatta, Takahiro</au><au>Shibata, Hirofumi</au><au>Fukui, Takayuki</au><au>Chen‐Yoshikawa, Toyofumi Fengshi</au><au>Nagano, Kazuki</au><au>Murate, Takashi</au><au>Kawamoto, Yoshiyuki</au><au>Tomida, Shuta</au><au>Takahashi, Takashi</au><au>Suzuki, Motoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2021-07</date><risdate>2021</risdate><volume>112</volume><issue>7</issue><spage>2770</spage><epage>2780</epage><pages>2770-2780</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y‐box as a cis‐acting element. As a parallel analysis of database records for 149 non–small‐cell lung cancer (NSCLC) cancer patients, we screened for trans‐acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer‐binding protein γ (CEBPγ) or Y‐box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide‐dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y‐box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.
Schematic illustration showing CEBPγ functions for cancer cell migration.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>33934437</pmid><doi>10.1111/cas.14928</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0682-5006</orcidid><orcidid>https://orcid.org/0000-0003-0615-7001</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Antibodies B cells Binding sites Cancer therapies CEBPγ Cell adhesion & migration Cell migration Ceramide CERS6 DNA binding proteins Enzymes Ethylenediaminetetraacetic acid Experiments Gene expression Invasiveness Kinases Lamellipodia Leukemia Lipids Luciferase Lung cancer Lung cancer, Non-small cell Medical prognosis Metabolism Metastases Metastasis Mutagenesis Non-small cell lung carcinoma Original Pathogenesis Protein binding Proteins Pseudopodia Transcription factors YBX1 |
| title | CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation |
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