Vasohibin‐2 is required for epithelial–mesenchymal transition of ovarian cancer cells by modulating transforming growth factor‐β signaling
Vasohibin‐2 (VASH2) is a homolog of VASH1, an endothelium‐derived angiogenesis inhibitor. Vasohibin‐2 is mainly expressed in cancer cells, and has been implicated in the progression of cancer by inducing angiogenesis and tumor growth. Although VASH2 has been recently reported to be involved in epith...
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| Veröffentlicht in: | Cancer science 2017-03, Vol.108 (3), p.419-426 |
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| creator | Norita, Rie Suzuki, Yasuhiro Furutani, Yutaka Takahashi, Kazuki Yoshimatsu, Yasuhiro Podyma‐Inoue, Katarzyna A. Watabe, Tetsuro Sato, Yasufumi |
| description | Vasohibin‐2 (VASH2) is a homolog of VASH1, an endothelium‐derived angiogenesis inhibitor. Vasohibin‐2 is mainly expressed in cancer cells, and has been implicated in the progression of cancer by inducing angiogenesis and tumor growth. Although VASH2 has been recently reported to be involved in epithelial–mesenchymal transition (EMT), its precise roles are obscure. The aim of the present study was to clarify the role of VASH2 in the EMT of cancer cells in relation to transforming growth factor‐β (TGF‐β) signaling, which is a major stimulator of EMT. Decreased expression of VASH2 in ovarian cancer cells significantly repressed the expression of TGF‐β type I receptor, namely activin receptor‐like kinase 5. Transforming growth factor‐β1‐induced phosphorylation of Smad2 and Smad3 was markedly decreased in VASH2 knockdown cells while the expression of Smad2 and Smad3 was unchanged. Accordingly, the responses to TGF‐β1 shown by promoter assay and plasminogen activator inhibitor type 1 expression were significantly attenuated in VASH2 knockdown cells. Furthermore, knockdown of VASH2 in cancer cells abrogated the TGF‐β1‐induced reduced expression of epithelial markers including E‐cadherin, and the elevated expression of mesenchymal markers including fibronectin, ZEB2, and Snail2, suggesting that endogenous VASH2 is required for TGF‐β1‐induced EMT. In accordance with these results, the effects of TGF‐β1 on cell morphology, migration, invasion, and MMP2 expression were also abrogated when VASH2 was knocked down. These results indicate that VASH2 played a significant role in the EMT by modulating the TGF‐β signaling. We propose that VASH2 would be a novel molecular target for the prevention of EMT in cancers.
Vasohibin‐2 (VASH2) is expressed by various cancer cells including ovarian cancer cells, which acts as angiogenesis stimulator. In the present study, we examined the possible role of VASH2 in the EMT of cancer cells, and found that VASH2 played a significant role in the EMT by modulating the expression of TGF‐β receptor 1 (ALK5) for TGF‐β signaling. |
| doi_str_mv | 10.1111/cas.13157 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5378260</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1856864544</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5007-957f871641ad60c843f84fa089ffbe54bdb4e09d94ec648d1226dc64eefcfa803</originalsourceid><addsrcrecordid>eNqNksFqFTEUhgdRbK0ufAEJuKmL2yaZTCazEcpFrVBwoXUbMpmTOymZ5DaZabm7PoLim_ggPkSfpLmdWlQomE1OOF_-nD_8RfGS4AOS16FW6YCUpKofFbukZM2ixpg_vq3rRYNLulM8S-kM45Kzhj0tdqjAnLGa7Bbfv6oUettaf331jSKbUITzyUbokAkRwdqOPTir3PXVjwESeN1vBuXQGJVPdrTBo2BQuFDRKo-08hoi0uBcQu0GDaGbnBqtX80XsuSwPaxiuBx7ZJQeQ8wP__qJkl155XLzefHEKJfgxd2-V5y-f_dlebw4-fTh4_LoZKErjLOtqjaiJpwR1XGsBSuNYEZh0RjTQsXarmWAm65hoDkTHaGUd7kCMNoogcu94u2su57aAToNPo_o5DraQcWNDMrKvzve9nIVLmRV1oLyrcD-nUAM5xOkUQ42ba0rD2FKkoiGCEHrhvwHWnHBWcVYRl__g56FKeavSZJS0dSC0arM1JuZ0jGkFMHcz02w3GZC5kzI20xk9tWfRu_J3yHIwOEMXFoHm4eV5PLo8yx5A_w8yFQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2289784253</pqid></control><display><type>article</type><title>Vasohibin‐2 is required for epithelial–mesenchymal transition of ovarian cancer cells by modulating transforming growth factor‐β signaling</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>PubMed Central</source><creator>Norita, Rie ; Suzuki, Yasuhiro ; Furutani, Yutaka ; Takahashi, Kazuki ; Yoshimatsu, Yasuhiro ; Podyma‐Inoue, Katarzyna A. ; Watabe, Tetsuro ; Sato, Yasufumi</creator><creatorcontrib>Norita, Rie ; Suzuki, Yasuhiro ; Furutani, Yutaka ; Takahashi, Kazuki ; Yoshimatsu, Yasuhiro ; Podyma‐Inoue, Katarzyna A. ; Watabe, Tetsuro ; Sato, Yasufumi</creatorcontrib><description>Vasohibin‐2 (VASH2) is a homolog of VASH1, an endothelium‐derived angiogenesis inhibitor. Vasohibin‐2 is mainly expressed in cancer cells, and has been implicated in the progression of cancer by inducing angiogenesis and tumor growth. Although VASH2 has been recently reported to be involved in epithelial–mesenchymal transition (EMT), its precise roles are obscure. The aim of the present study was to clarify the role of VASH2 in the EMT of cancer cells in relation to transforming growth factor‐β (TGF‐β) signaling, which is a major stimulator of EMT. Decreased expression of VASH2 in ovarian cancer cells significantly repressed the expression of TGF‐β type I receptor, namely activin receptor‐like kinase 5. Transforming growth factor‐β1‐induced phosphorylation of Smad2 and Smad3 was markedly decreased in VASH2 knockdown cells while the expression of Smad2 and Smad3 was unchanged. Accordingly, the responses to TGF‐β1 shown by promoter assay and plasminogen activator inhibitor type 1 expression were significantly attenuated in VASH2 knockdown cells. Furthermore, knockdown of VASH2 in cancer cells abrogated the TGF‐β1‐induced reduced expression of epithelial markers including E‐cadherin, and the elevated expression of mesenchymal markers including fibronectin, ZEB2, and Snail2, suggesting that endogenous VASH2 is required for TGF‐β1‐induced EMT. In accordance with these results, the effects of TGF‐β1 on cell morphology, migration, invasion, and MMP2 expression were also abrogated when VASH2 was knocked down. These results indicate that VASH2 played a significant role in the EMT by modulating the TGF‐β signaling. We propose that VASH2 would be a novel molecular target for the prevention of EMT in cancers.
Vasohibin‐2 (VASH2) is expressed by various cancer cells including ovarian cancer cells, which acts as angiogenesis stimulator. In the present study, we examined the possible role of VASH2 in the EMT of cancer cells, and found that VASH2 played a significant role in the EMT by modulating the expression of TGF‐β receptor 1 (ALK5) for TGF‐β signaling.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.13157</identifier><identifier>PMID: 28064471</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Activin ; Adenoviruses ; ALK5 ; Angiogenesis ; Angiogenesis inhibitors ; Angiogenic Proteins - genetics ; Cadherins - biosynthesis ; Cell Line, Tumor ; Cell migration ; Cell Proliferation - genetics ; Cytokines ; Cytology ; EMT ; Endothelium ; Epithelial-Mesenchymal Transition - genetics ; Female ; Fibronectin ; Fibronectins - biosynthesis ; Gelatinase A ; Genes ; Growth factors ; Homeodomain Proteins - biosynthesis ; Humans ; Immunoglobulins ; Kinases ; Laboratories ; Liver cancer ; Matrix Metalloproteinase 2 - biosynthesis ; Mesenchyme ; MicroRNAs ; Morphology ; Neovascularization, Pathologic - genetics ; Original ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Phosphorylation ; Phosphorylation - genetics ; Plasminogen Activator Inhibitor 1 - biosynthesis ; Plasminogen activator inhibitors ; Protein-Serine-Threonine Kinases - biosynthesis ; Proteins ; Receptor, Transforming Growth Factor-beta Type I ; Receptors, Transforming Growth Factor beta - biosynthesis ; Repressor Proteins - biosynthesis ; RNA Interference ; RNA, Small Interfering - genetics ; Signal Transduction - genetics ; Smad2 protein ; Smad2 Protein - metabolism ; Smad3 protein ; Smad3 Protein - metabolism ; Snail Family Transcription Factors - biosynthesis ; TGF‐β ; Transforming Growth Factor beta - metabolism ; Transforming growth factor-b ; Transforming growth factor-b1 ; vasohibin‐2 ; Zinc Finger E-box Binding Homeobox 2</subject><ispartof>Cancer science, 2017-03, Vol.108 (3), p.419-426</ispartof><rights>2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2017. 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-c5007-957f871641ad60c843f84fa089ffbe54bdb4e09d94ec648d1226dc64eefcfa803</citedby><cites>FETCH-LOGICAL-c5007-957f871641ad60c843f84fa089ffbe54bdb4e09d94ec648d1226dc64eefcfa803</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/PMC5378260/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378260/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28064471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Norita, Rie</creatorcontrib><creatorcontrib>Suzuki, Yasuhiro</creatorcontrib><creatorcontrib>Furutani, Yutaka</creatorcontrib><creatorcontrib>Takahashi, Kazuki</creatorcontrib><creatorcontrib>Yoshimatsu, Yasuhiro</creatorcontrib><creatorcontrib>Podyma‐Inoue, Katarzyna A.</creatorcontrib><creatorcontrib>Watabe, Tetsuro</creatorcontrib><creatorcontrib>Sato, Yasufumi</creatorcontrib><title>Vasohibin‐2 is required for epithelial–mesenchymal transition of ovarian cancer cells by modulating transforming growth factor‐β signaling</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Vasohibin‐2 (VASH2) is a homolog of VASH1, an endothelium‐derived angiogenesis inhibitor. Vasohibin‐2 is mainly expressed in cancer cells, and has been implicated in the progression of cancer by inducing angiogenesis and tumor growth. Although VASH2 has been recently reported to be involved in epithelial–mesenchymal transition (EMT), its precise roles are obscure. The aim of the present study was to clarify the role of VASH2 in the EMT of cancer cells in relation to transforming growth factor‐β (TGF‐β) signaling, which is a major stimulator of EMT. Decreased expression of VASH2 in ovarian cancer cells significantly repressed the expression of TGF‐β type I receptor, namely activin receptor‐like kinase 5. Transforming growth factor‐β1‐induced phosphorylation of Smad2 and Smad3 was markedly decreased in VASH2 knockdown cells while the expression of Smad2 and Smad3 was unchanged. Accordingly, the responses to TGF‐β1 shown by promoter assay and plasminogen activator inhibitor type 1 expression were significantly attenuated in VASH2 knockdown cells. Furthermore, knockdown of VASH2 in cancer cells abrogated the TGF‐β1‐induced reduced expression of epithelial markers including E‐cadherin, and the elevated expression of mesenchymal markers including fibronectin, ZEB2, and Snail2, suggesting that endogenous VASH2 is required for TGF‐β1‐induced EMT. In accordance with these results, the effects of TGF‐β1 on cell morphology, migration, invasion, and MMP2 expression were also abrogated when VASH2 was knocked down. These results indicate that VASH2 played a significant role in the EMT by modulating the TGF‐β signaling. We propose that VASH2 would be a novel molecular target for the prevention of EMT in cancers.
Vasohibin‐2 (VASH2) is expressed by various cancer cells including ovarian cancer cells, which acts as angiogenesis stimulator. In the present study, we examined the possible role of VASH2 in the EMT of cancer cells, and found that VASH2 played a significant role in the EMT by modulating the expression of TGF‐β receptor 1 (ALK5) for TGF‐β signaling.</description><subject>Activin</subject><subject>Adenoviruses</subject><subject>ALK5</subject><subject>Angiogenesis</subject><subject>Angiogenesis inhibitors</subject><subject>Angiogenic Proteins - genetics</subject><subject>Cadherins - biosynthesis</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Proliferation - genetics</subject><subject>Cytokines</subject><subject>Cytology</subject><subject>EMT</subject><subject>Endothelium</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Female</subject><subject>Fibronectin</subject><subject>Fibronectins - biosynthesis</subject><subject>Gelatinase A</subject><subject>Genes</subject><subject>Growth factors</subject><subject>Homeodomain Proteins - biosynthesis</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Liver cancer</subject><subject>Matrix Metalloproteinase 2 - biosynthesis</subject><subject>Mesenchyme</subject><subject>MicroRNAs</subject><subject>Morphology</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Original</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Phosphorylation</subject><subject>Phosphorylation - genetics</subject><subject>Plasminogen Activator Inhibitor 1 - biosynthesis</subject><subject>Plasminogen activator inhibitors</subject><subject>Protein-Serine-Threonine Kinases - biosynthesis</subject><subject>Proteins</subject><subject>Receptor, Transforming Growth Factor-beta Type I</subject><subject>Receptors, Transforming Growth Factor beta - biosynthesis</subject><subject>Repressor Proteins - biosynthesis</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signal Transduction - genetics</subject><subject>Smad2 protein</subject><subject>Smad2 Protein - metabolism</subject><subject>Smad3 protein</subject><subject>Smad3 Protein - metabolism</subject><subject>Snail Family Transcription Factors - biosynthesis</subject><subject>TGF‐β</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Transforming growth factor-b</subject><subject>Transforming growth factor-b1</subject><subject>vasohibin‐2</subject><subject>Zinc Finger E-box Binding Homeobox 2</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNksFqFTEUhgdRbK0ufAEJuKmL2yaZTCazEcpFrVBwoXUbMpmTOymZ5DaZabm7PoLim_ggPkSfpLmdWlQomE1OOF_-nD_8RfGS4AOS16FW6YCUpKofFbukZM2ixpg_vq3rRYNLulM8S-kM45Kzhj0tdqjAnLGa7Bbfv6oUettaf331jSKbUITzyUbokAkRwdqOPTir3PXVjwESeN1vBuXQGJVPdrTBo2BQuFDRKo-08hoi0uBcQu0GDaGbnBqtX80XsuSwPaxiuBx7ZJQeQ8wP__qJkl155XLzefHEKJfgxd2-V5y-f_dlebw4-fTh4_LoZKErjLOtqjaiJpwR1XGsBSuNYEZh0RjTQsXarmWAm65hoDkTHaGUd7kCMNoogcu94u2su57aAToNPo_o5DraQcWNDMrKvzve9nIVLmRV1oLyrcD-nUAM5xOkUQ42ba0rD2FKkoiGCEHrhvwHWnHBWcVYRl__g56FKeavSZJS0dSC0arM1JuZ0jGkFMHcz02w3GZC5kzI20xk9tWfRu_J3yHIwOEMXFoHm4eV5PLo8yx5A_w8yFQ</recordid><startdate>201703</startdate><enddate>201703</enddate><creator>Norita, Rie</creator><creator>Suzuki, Yasuhiro</creator><creator>Furutani, Yutaka</creator><creator>Takahashi, Kazuki</creator><creator>Yoshimatsu, Yasuhiro</creator><creator>Podyma‐Inoue, Katarzyna A.</creator><creator>Watabe, Tetsuro</creator><creator>Sato, Yasufumi</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>8FE</scope><scope>8FH</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>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>201703</creationdate><title>Vasohibin‐2 is required for epithelial–mesenchymal transition of ovarian cancer cells by modulating transforming growth factor‐β signaling</title><author>Norita, Rie ; Suzuki, Yasuhiro ; Furutani, Yutaka ; Takahashi, Kazuki ; Yoshimatsu, Yasuhiro ; Podyma‐Inoue, Katarzyna A. ; Watabe, Tetsuro ; Sato, Yasufumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5007-957f871641ad60c843f84fa089ffbe54bdb4e09d94ec648d1226dc64eefcfa803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Activin</topic><topic>Adenoviruses</topic><topic>ALK5</topic><topic>Angiogenesis</topic><topic>Angiogenesis inhibitors</topic><topic>Angiogenic Proteins - genetics</topic><topic>Cadherins - biosynthesis</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Proliferation - genetics</topic><topic>Cytokines</topic><topic>Cytology</topic><topic>EMT</topic><topic>Endothelium</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Female</topic><topic>Fibronectin</topic><topic>Fibronectins - biosynthesis</topic><topic>Gelatinase A</topic><topic>Genes</topic><topic>Growth factors</topic><topic>Homeodomain Proteins - biosynthesis</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Liver cancer</topic><topic>Matrix Metalloproteinase 2 - biosynthesis</topic><topic>Mesenchyme</topic><topic>MicroRNAs</topic><topic>Morphology</topic><topic>Neovascularization, Pathologic - genetics</topic><topic>Original</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Phosphorylation</topic><topic>Phosphorylation - genetics</topic><topic>Plasminogen Activator Inhibitor 1 - biosynthesis</topic><topic>Plasminogen activator inhibitors</topic><topic>Protein-Serine-Threonine Kinases - biosynthesis</topic><topic>Proteins</topic><topic>Receptor, Transforming Growth Factor-beta Type I</topic><topic>Receptors, Transforming Growth Factor beta - biosynthesis</topic><topic>Repressor Proteins - biosynthesis</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signal Transduction - genetics</topic><topic>Smad2 protein</topic><topic>Smad2 Protein - metabolism</topic><topic>Smad3 protein</topic><topic>Smad3 Protein - metabolism</topic><topic>Snail Family Transcription Factors - biosynthesis</topic><topic>TGF‐β</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Transforming growth factor-b</topic><topic>Transforming growth factor-b1</topic><topic>vasohibin‐2</topic><topic>Zinc Finger E-box Binding Homeobox 2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Norita, Rie</creatorcontrib><creatorcontrib>Suzuki, Yasuhiro</creatorcontrib><creatorcontrib>Furutani, Yutaka</creatorcontrib><creatorcontrib>Takahashi, Kazuki</creatorcontrib><creatorcontrib>Yoshimatsu, Yasuhiro</creatorcontrib><creatorcontrib>Podyma‐Inoue, Katarzyna A.</creatorcontrib><creatorcontrib>Watabe, Tetsuro</creatorcontrib><creatorcontrib>Sato, Yasufumi</creatorcontrib><collection>Wiley Online Library Open Access</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 SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</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>MEDLINE - Academic</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Norita, Rie</au><au>Suzuki, Yasuhiro</au><au>Furutani, Yutaka</au><au>Takahashi, Kazuki</au><au>Yoshimatsu, Yasuhiro</au><au>Podyma‐Inoue, Katarzyna A.</au><au>Watabe, Tetsuro</au><au>Sato, Yasufumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vasohibin‐2 is required for epithelial–mesenchymal transition of ovarian cancer cells by modulating transforming growth factor‐β signaling</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2017-03</date><risdate>2017</risdate><volume>108</volume><issue>3</issue><spage>419</spage><epage>426</epage><pages>419-426</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Vasohibin‐2 (VASH2) is a homolog of VASH1, an endothelium‐derived angiogenesis inhibitor. Vasohibin‐2 is mainly expressed in cancer cells, and has been implicated in the progression of cancer by inducing angiogenesis and tumor growth. Although VASH2 has been recently reported to be involved in epithelial–mesenchymal transition (EMT), its precise roles are obscure. The aim of the present study was to clarify the role of VASH2 in the EMT of cancer cells in relation to transforming growth factor‐β (TGF‐β) signaling, which is a major stimulator of EMT. Decreased expression of VASH2 in ovarian cancer cells significantly repressed the expression of TGF‐β type I receptor, namely activin receptor‐like kinase 5. Transforming growth factor‐β1‐induced phosphorylation of Smad2 and Smad3 was markedly decreased in VASH2 knockdown cells while the expression of Smad2 and Smad3 was unchanged. Accordingly, the responses to TGF‐β1 shown by promoter assay and plasminogen activator inhibitor type 1 expression were significantly attenuated in VASH2 knockdown cells. Furthermore, knockdown of VASH2 in cancer cells abrogated the TGF‐β1‐induced reduced expression of epithelial markers including E‐cadherin, and the elevated expression of mesenchymal markers including fibronectin, ZEB2, and Snail2, suggesting that endogenous VASH2 is required for TGF‐β1‐induced EMT. In accordance with these results, the effects of TGF‐β1 on cell morphology, migration, invasion, and MMP2 expression were also abrogated when VASH2 was knocked down. These results indicate that VASH2 played a significant role in the EMT by modulating the TGF‐β signaling. We propose that VASH2 would be a novel molecular target for the prevention of EMT in cancers.
Vasohibin‐2 (VASH2) is expressed by various cancer cells including ovarian cancer cells, which acts as angiogenesis stimulator. In the present study, we examined the possible role of VASH2 in the EMT of cancer cells, and found that VASH2 played a significant role in the EMT by modulating the expression of TGF‐β receptor 1 (ALK5) for TGF‐β signaling.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>28064471</pmid><doi>10.1111/cas.13157</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer science, 2017-03, Vol.108 (3), p.419-426 |
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| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; PubMed Central |
| subjects | Activin Adenoviruses ALK5 Angiogenesis Angiogenesis inhibitors Angiogenic Proteins - genetics Cadherins - biosynthesis Cell Line, Tumor Cell migration Cell Proliferation - genetics Cytokines Cytology EMT Endothelium Epithelial-Mesenchymal Transition - genetics Female Fibronectin Fibronectins - biosynthesis Gelatinase A Genes Growth factors Homeodomain Proteins - biosynthesis Humans Immunoglobulins Kinases Laboratories Liver cancer Matrix Metalloproteinase 2 - biosynthesis Mesenchyme MicroRNAs Morphology Neovascularization, Pathologic - genetics Original Ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Phosphorylation Phosphorylation - genetics Plasminogen Activator Inhibitor 1 - biosynthesis Plasminogen activator inhibitors Protein-Serine-Threonine Kinases - biosynthesis Proteins Receptor, Transforming Growth Factor-beta Type I Receptors, Transforming Growth Factor beta - biosynthesis Repressor Proteins - biosynthesis RNA Interference RNA, Small Interfering - genetics Signal Transduction - genetics Smad2 protein Smad2 Protein - metabolism Smad3 protein Smad3 Protein - metabolism Snail Family Transcription Factors - biosynthesis TGF‐β Transforming Growth Factor beta - metabolism Transforming growth factor-b Transforming growth factor-b1 vasohibin‐2 Zinc Finger E-box Binding Homeobox 2 |
| title | Vasohibin‐2 is required for epithelial–mesenchymal transition of ovarian cancer cells by modulating transforming growth factor‐β signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T06%3A28%3A18IST&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=Vasohibin%E2%80%902%20is%20required%20for%20epithelial%E2%80%93mesenchymal%20transition%20of%20ovarian%20cancer%20cells%20by%20modulating%20transforming%20growth%20factor%E2%80%90%CE%B2%20signaling&rft.jtitle=Cancer%20science&rft.au=Norita,%20Rie&rft.date=2017-03&rft.volume=108&rft.issue=3&rft.spage=419&rft.epage=426&rft.pages=419-426&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.13157&rft_dat=%3Cproquest_pubme%3E1856864544%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=2289784253&rft_id=info:pmid/28064471&rfr_iscdi=true |