Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism
Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified. In this study, we detected YY1 expressio...
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| Veröffentlicht in: | Molecular cancer 2014-05, Vol.13 (1), p.130-130, Article 130 |
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| creator | Zhang, Jing-Jing Zhu, Yi Xie, Kun-Ling Peng, Yun-Peng Tao, Jin-Qiu Tang, Jie Li, Zheng Xu, Ze-Kuan Dai, Cun-Cai Qian, Zhu-Yin Jiang, Kui-Rong Wu, Jun-Li Gao, Wen-Tao Du, Qing Miao, Yi |
| description | Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified.
In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software.
We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.
The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC. |
| doi_str_mv | 10.1186/1476-4598-13-130 |
| format | Article |
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In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software.
We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.
The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.</description><identifier>ISSN: 1476-4598</identifier><identifier>EISSN: 1476-4598</identifier><identifier>DOI: 10.1186/1476-4598-13-130</identifier><identifier>PMID: 24884523</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Analysis ; Animals ; Binding sites ; Cancer ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - metabolism ; Carcinoma, Pancreatic Ductal - mortality ; Carcinoma, Pancreatic Ductal - secondary ; Chemotherapy ; Clinical medicine ; Confidence intervals ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; Hospitals ; Humans ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - mortality ; Liver Neoplasms - secondary ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - mortality ; Lung Neoplasms - secondary ; Male ; Matrix Metalloproteinase 10 - genetics ; Matrix Metalloproteinase 10 - metabolism ; Medical prognosis ; MEF2 Transcription Factors - genetics ; MEF2 Transcription Factors - metabolism ; Metastasis ; Mice ; Mice, Nude ; Middle Aged ; Mucin-4 - genetics ; Mucin-4 - metabolism ; p38 Mitogen-Activated Protein Kinases - genetics ; p38 Mitogen-Activated Protein Kinases - metabolism ; Pancreas ; Pancreas - metabolism ; Pancreas - pathology ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Physiological aspects ; Protein expression ; Proteins ; Receptor, ErbB-2 - genetics ; Receptor, ErbB-2 - metabolism ; Rodents ; Signal Transduction ; Studies ; Survival Analysis ; Tumorigenesis ; Tumors ; Xenograft Model Antitumor Assays ; YY1 Transcription Factor - genetics ; YY1 Transcription Factor - metabolism</subject><ispartof>Molecular cancer, 2014-05, Vol.13 (1), p.130-130, Article 130</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Zhang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Copyright © 2014 Zhang et al.; licensee BioMed Central Ltd. 2014 Zhang et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b617t-fc5f484dd0e1399ae41f13ef40fddb25769e3afe69c63b99e361b25002d69a943</citedby><cites>FETCH-LOGICAL-b617t-fc5f484dd0e1399ae41f13ef40fddb25769e3afe69c63b99e361b25002d69a943</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/PMC4047260/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047260/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24884523$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Jing-Jing</creatorcontrib><creatorcontrib>Zhu, Yi</creatorcontrib><creatorcontrib>Xie, Kun-Ling</creatorcontrib><creatorcontrib>Peng, Yun-Peng</creatorcontrib><creatorcontrib>Tao, Jin-Qiu</creatorcontrib><creatorcontrib>Tang, Jie</creatorcontrib><creatorcontrib>Li, Zheng</creatorcontrib><creatorcontrib>Xu, Ze-Kuan</creatorcontrib><creatorcontrib>Dai, Cun-Cai</creatorcontrib><creatorcontrib>Qian, Zhu-Yin</creatorcontrib><creatorcontrib>Jiang, Kui-Rong</creatorcontrib><creatorcontrib>Wu, Jun-Li</creatorcontrib><creatorcontrib>Gao, Wen-Tao</creatorcontrib><creatorcontrib>Du, Qing</creatorcontrib><creatorcontrib>Miao, Yi</creatorcontrib><title>Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism</title><title>Molecular cancer</title><addtitle>Mol Cancer</addtitle><description>Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified.
In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software.
We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.
The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Animals</subject><subject>Binding sites</subject><subject>Cancer</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - metabolism</subject><subject>Carcinoma, Pancreatic Ductal - mortality</subject><subject>Carcinoma, Pancreatic Ductal - secondary</subject><subject>Chemotherapy</subject><subject>Clinical medicine</subject><subject>Confidence intervals</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - secondary</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - secondary</subject><subject>Male</subject><subject>Matrix Metalloproteinase 10 - genetics</subject><subject>Matrix Metalloproteinase 10 - metabolism</subject><subject>Medical prognosis</subject><subject>MEF2 Transcription Factors - genetics</subject><subject>MEF2 Transcription Factors - metabolism</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Mucin-4 - genetics</subject><subject>Mucin-4 - metabolism</subject><subject>p38 Mitogen-Activated Protein Kinases - genetics</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Pancreas</subject><subject>Pancreas - metabolism</subject><subject>Pancreas - pathology</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Physiological aspects</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Studies</subject><subject>Survival Analysis</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><subject>YY1 Transcription Factor - genetics</subject><subject>YY1 Transcription Factor - metabolism</subject><issn>1476-4598</issn><issn>1476-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1Uk1v1DAQjRCIlsKdE7LEhUu6duw4yQWpjbaA1BUc6KEny7HHW1eJHeykqL-Ev4ujLUsXFXkk2zNv3nxm2VuCTwmp-YqwiuesbOqc0CT4WXa8Vz1_9D7KXsV4izGp6oq9zI4KVtesLOhx9uvaOnQt3TYnKM7jGCBGiMi6Oxmtd0g6jQaYZExiI_IGjdKpAHKyCulZTbJHUoPzSgZlnR8k6u6R9j9dgO3cJ5jbos3mG8GJE0m0uWrZah2682I10nq1WV8Uba5hBJdIphRK3Uhn4_A6e2FkH-HNw32SXV2sv7ef88uvn760Z5d5x0k15UaVhtVMawyENo0ERgyhYBg2WndFWfEGqDTAG8Vp16QPJ0mNcaF5IxtGT7KPO95x7gbQKiURZC_GYAcZ7oWXVhxanL0RW38nGGZVwXEiaHcEnfX_ITi0KD-IZTBiGYwgNMnC8uEhjeB_zBAnMdiooO-lAz9HQUrKCE5p0wR9_w_01s_BpSYtqJpwxmj5F7WVPQjrjE_B1UIqzkracFZW9YI6fQKVjobBKu_A2KQ_cMA7BxV8jAHMvlCCxbKST5X27nGH9w5_dpD-Brrm2-I</recordid><startdate>20140529</startdate><enddate>20140529</enddate><creator>Zhang, Jing-Jing</creator><creator>Zhu, Yi</creator><creator>Xie, Kun-Ling</creator><creator>Peng, Yun-Peng</creator><creator>Tao, Jin-Qiu</creator><creator>Tang, Jie</creator><creator>Li, Zheng</creator><creator>Xu, Ze-Kuan</creator><creator>Dai, Cun-Cai</creator><creator>Qian, Zhu-Yin</creator><creator>Jiang, Kui-Rong</creator><creator>Wu, Jun-Li</creator><creator>Gao, Wen-Tao</creator><creator>Du, Qing</creator><creator>Miao, Yi</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><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>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140529</creationdate><title>Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism</title><author>Zhang, Jing-Jing ; Zhu, Yi ; Xie, Kun-Ling ; Peng, Yun-Peng ; Tao, Jin-Qiu ; Tang, Jie ; Li, Zheng ; Xu, Ze-Kuan ; Dai, Cun-Cai ; Qian, Zhu-Yin ; Jiang, Kui-Rong ; Wu, Jun-Li ; Gao, Wen-Tao ; Du, Qing ; Miao, Yi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b617t-fc5f484dd0e1399ae41f13ef40fddb25769e3afe69c63b99e361b25002d69a943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Animals</topic><topic>Binding sites</topic><topic>Cancer</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - metabolism</topic><topic>Carcinoma, Pancreatic Ductal - mortality</topic><topic>Carcinoma, Pancreatic Ductal - secondary</topic><topic>Chemotherapy</topic><topic>Clinical medicine</topic><topic>Confidence intervals</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - mortality</topic><topic>Liver Neoplasms - secondary</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - secondary</topic><topic>Male</topic><topic>Matrix Metalloproteinase 10 - genetics</topic><topic>Matrix Metalloproteinase 10 - metabolism</topic><topic>Medical prognosis</topic><topic>MEF2 Transcription Factors - genetics</topic><topic>MEF2 Transcription Factors - metabolism</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Mucin-4 - genetics</topic><topic>Mucin-4 - metabolism</topic><topic>p38 Mitogen-Activated Protein Kinases - genetics</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Pancreas</topic><topic>Pancreas - metabolism</topic><topic>Pancreas - pathology</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Physiological aspects</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Studies</topic><topic>Survival Analysis</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><topic>YY1 Transcription Factor - genetics</topic><topic>YY1 Transcription Factor - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jing-Jing</creatorcontrib><creatorcontrib>Zhu, Yi</creatorcontrib><creatorcontrib>Xie, Kun-Ling</creatorcontrib><creatorcontrib>Peng, Yun-Peng</creatorcontrib><creatorcontrib>Tao, Jin-Qiu</creatorcontrib><creatorcontrib>Tang, Jie</creatorcontrib><creatorcontrib>Li, Zheng</creatorcontrib><creatorcontrib>Xu, Ze-Kuan</creatorcontrib><creatorcontrib>Dai, Cun-Cai</creatorcontrib><creatorcontrib>Qian, Zhu-Yin</creatorcontrib><creatorcontrib>Jiang, Kui-Rong</creatorcontrib><creatorcontrib>Wu, Jun-Li</creatorcontrib><creatorcontrib>Gao, Wen-Tao</creatorcontrib><creatorcontrib>Du, Qing</creatorcontrib><creatorcontrib>Miao, Yi</creatorcontrib><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>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Central</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>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>PubMed Central (Full Participant titles)</collection><jtitle>Molecular cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Jing-Jing</au><au>Zhu, Yi</au><au>Xie, Kun-Ling</au><au>Peng, Yun-Peng</au><au>Tao, Jin-Qiu</au><au>Tang, Jie</au><au>Li, Zheng</au><au>Xu, Ze-Kuan</au><au>Dai, Cun-Cai</au><au>Qian, Zhu-Yin</au><au>Jiang, Kui-Rong</au><au>Wu, Jun-Li</au><au>Gao, Wen-Tao</au><au>Du, Qing</au><au>Miao, Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism</atitle><jtitle>Molecular cancer</jtitle><addtitle>Mol Cancer</addtitle><date>2014-05-29</date><risdate>2014</risdate><volume>13</volume><issue>1</issue><spage>130</spage><epage>130</epage><pages>130-130</pages><artnum>130</artnum><issn>1476-4598</issn><eissn>1476-4598</eissn><abstract>Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified.
In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software.
We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.
The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24884523</pmid><doi>10.1186/1476-4598-13-130</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1476-4598 |
| ispartof | Molecular cancer, 2014-05, Vol.13 (1), p.130-130, Article 130 |
| issn | 1476-4598 1476-4598 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4047260 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SpringerLink Journals - AutoHoldings; PubMed Central Open Access; Springer Nature OA Free Journals |
| subjects | Adult Aged Aged, 80 and over Analysis Animals Binding sites Cancer Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - metabolism Carcinoma, Pancreatic Ductal - mortality Carcinoma, Pancreatic Ductal - secondary Chemotherapy Clinical medicine Confidence intervals Female Gene expression Gene Expression Regulation, Neoplastic Genes Genetic aspects Hospitals Humans Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - mortality Liver Neoplasms - secondary Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - mortality Lung Neoplasms - secondary Male Matrix Metalloproteinase 10 - genetics Matrix Metalloproteinase 10 - metabolism Medical prognosis MEF2 Transcription Factors - genetics MEF2 Transcription Factors - metabolism Metastasis Mice Mice, Nude Middle Aged Mucin-4 - genetics Mucin-4 - metabolism p38 Mitogen-Activated Protein Kinases - genetics p38 Mitogen-Activated Protein Kinases - metabolism Pancreas Pancreas - metabolism Pancreas - pathology Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Physiological aspects Protein expression Proteins Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism Rodents Signal Transduction Studies Survival Analysis Tumorigenesis Tumors Xenograft Model Antitumor Assays YY1 Transcription Factor - genetics YY1 Transcription Factor - metabolism |
| title | Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T06%3A33%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Yin%20Yang-1%20suppresses%20invasion%20and%20metastasis%20of%20pancreatic%20ductal%20adenocarcinoma%20by%20downregulating%20MMP10%20in%20a%20MUC4/ErbB2/p38/MEF2C-dependent%20mechanism&rft.jtitle=Molecular%20cancer&rft.au=Zhang,%20Jing-Jing&rft.date=2014-05-29&rft.volume=13&rft.issue=1&rft.spage=130&rft.epage=130&rft.pages=130-130&rft.artnum=130&rft.issn=1476-4598&rft.eissn=1476-4598&rft_id=info:doi/10.1186/1476-4598-13-130&rft_dat=%3Cgale_pubme%3EA539645785%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1538164435&rft_id=info:pmid/24884523&rft_galeid=A539645785&rfr_iscdi=true |