Heat shock factor 1 promotes invasion and metastasis of hepatocellular carcinoma in vitro and in vivo

BACKGROUND: Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in hepatocellular carcinoma (HCC) remain unknown. METHODS: Quantitative reverse transcriptase‐polymerase chain reaction analysis, Western bl...

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Veröffentlicht in:Cancer 2012-04, Vol.118 (7), p.1782-1794
Hauptverfasser: Fang, Feng, Chang, Ruimin, Yang, Lianyue
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Chang, Ruimin
Yang, Lianyue
description BACKGROUND: Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in hepatocellular carcinoma (HCC) remain unknown. METHODS: Quantitative reverse transcriptase‐polymerase chain reaction analysis, Western blot analysis, and immunohistochemical staining were used to detect expression levels of HSF1, and its correlation with clinicopathologic parameters and the prognosis for patients with HCC were analyzed. In addition, the biologic function and molecular mechanisms of HSF1 in HCC were investigated in vitro and in vivo. RESULTS: HSF1 levels were elevated predominantly in HCC, especially in venous emboli from HCC (P < .05), and high expression levels of HSF1 were correlated significantly with multiple nodules, venous invasion, absence of capsular formation, and high Edmondson‐Steiner grade as well as poor overall survival and disease‐free survival in patients with HCC (P < .05). Multivariate Cox regression analysis revealed that high HSF1 expression was an independent prognostic factor for overall survival in patients with HCC (relative risk, 4.874; P < .001). Finally, HSF1 was capable of promoting HCC cell migration and invasion in vitro and in vivo by facilitating the expression and phosphorylation of heat shock protein 27. CONCLUSIONS: Collectively, the current findings suggested that HSF1 may serve as a novel prognostic marker and therapeutic target for HCC. Cancer 2012;. © 2011 American Cancer Society. Heat shock factor 1 (HSF1) is elevated predominantly in hepatocellular carcinoma (HCC) and is significantly correlated with metastatic potential and with the prognosis of patients with HCC after hepatic resection. In addition, HSF1 is capable of promoting HCC cell migration and invasion in vitro and in vivo by facilitating the expression and phosphorylation of heat shock protein 27, suggesting that HSF1 may serve as a novel prognostic marker and therapeutic target for HCC.
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However, the clinical significance and biologic function of HSF1 in hepatocellular carcinoma (HCC) remain unknown. METHODS: Quantitative reverse transcriptase‐polymerase chain reaction analysis, Western blot analysis, and immunohistochemical staining were used to detect expression levels of HSF1, and its correlation with clinicopathologic parameters and the prognosis for patients with HCC were analyzed. In addition, the biologic function and molecular mechanisms of HSF1 in HCC were investigated in vitro and in vivo. RESULTS: HSF1 levels were elevated predominantly in HCC, especially in venous emboli from HCC (P &lt; .05), and high expression levels of HSF1 were correlated significantly with multiple nodules, venous invasion, absence of capsular formation, and high Edmondson‐Steiner grade as well as poor overall survival and disease‐free survival in patients with HCC (P &lt; .05). Multivariate Cox regression analysis revealed that high HSF1 expression was an independent prognostic factor for overall survival in patients with HCC (relative risk, 4.874; P &lt; .001). Finally, HSF1 was capable of promoting HCC cell migration and invasion in vitro and in vivo by facilitating the expression and phosphorylation of heat shock protein 27. CONCLUSIONS: Collectively, the current findings suggested that HSF1 may serve as a novel prognostic marker and therapeutic target for HCC. Cancer 2012;. © 2011 American Cancer Society. Heat shock factor 1 (HSF1) is elevated predominantly in hepatocellular carcinoma (HCC) and is significantly correlated with metastatic potential and with the prognosis of patients with HCC after hepatic resection. In addition, HSF1 is capable of promoting HCC cell migration and invasion in vitro and in vivo by facilitating the expression and phosphorylation of heat shock protein 27, suggesting that HSF1 may serve as a novel prognostic marker and therapeutic target for HCC.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.26482</identifier><identifier>PMID: 22009757</identifier><identifier>CODEN: CANCAR</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult ; Aged ; Animals ; Biological and medical sciences ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - secondary ; DNA-Binding Proteins - metabolism ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; heat shock factor 1 ; heat shock protein 27 ; Heat Shock Transcription Factors ; hepatocellular carcinoma ; Humans ; invasion ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; metastasis ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Prognosis ; Transcription Factors - metabolism ; Tumors</subject><ispartof>Cancer, 2012-04, Vol.118 (7), p.1782-1794</ispartof><rights>Copyright © 2011 American Cancer Society</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 American Cancer Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4602-eab4c1dbc6e586df9e7e1c8543dd8c32b9480d6cc7614f4f9be5f23791e341a13</citedby><cites>FETCH-LOGICAL-c4602-eab4c1dbc6e586df9e7e1c8543dd8c32b9480d6cc7614f4f9be5f23791e341a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncr.26482$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncr.26482$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25665158$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22009757$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fang, Feng</creatorcontrib><creatorcontrib>Chang, Ruimin</creatorcontrib><creatorcontrib>Yang, Lianyue</creatorcontrib><title>Heat shock factor 1 promotes invasion and metastasis of hepatocellular carcinoma in vitro and in vivo</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND: Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in hepatocellular carcinoma (HCC) remain unknown. METHODS: Quantitative reverse transcriptase‐polymerase chain reaction analysis, Western blot analysis, and immunohistochemical staining were used to detect expression levels of HSF1, and its correlation with clinicopathologic parameters and the prognosis for patients with HCC were analyzed. In addition, the biologic function and molecular mechanisms of HSF1 in HCC were investigated in vitro and in vivo. RESULTS: HSF1 levels were elevated predominantly in HCC, especially in venous emboli from HCC (P &lt; .05), and high expression levels of HSF1 were correlated significantly with multiple nodules, venous invasion, absence of capsular formation, and high Edmondson‐Steiner grade as well as poor overall survival and disease‐free survival in patients with HCC (P &lt; .05). Multivariate Cox regression analysis revealed that high HSF1 expression was an independent prognostic factor for overall survival in patients with HCC (relative risk, 4.874; P &lt; .001). Finally, HSF1 was capable of promoting HCC cell migration and invasion in vitro and in vivo by facilitating the expression and phosphorylation of heat shock protein 27. CONCLUSIONS: Collectively, the current findings suggested that HSF1 may serve as a novel prognostic marker and therapeutic target for HCC. Cancer 2012;. © 2011 American Cancer Society. Heat shock factor 1 (HSF1) is elevated predominantly in hepatocellular carcinoma (HCC) and is significantly correlated with metastatic potential and with the prognosis of patients with HCC after hepatic resection. In addition, HSF1 is capable of promoting HCC cell migration and invasion in vitro and in vivo by facilitating the expression and phosphorylation of heat shock protein 27, suggesting that HSF1 may serve as a novel prognostic marker and therapeutic target for HCC.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - secondary</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>heat shock factor 1</subject><subject>heat shock protein 27</subject><subject>Heat Shock Transcription Factors</subject><subject>hepatocellular carcinoma</subject><subject>Humans</subject><subject>invasion</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Transplantation</subject><subject>Prognosis</subject><subject>Transcription Factors - metabolism</subject><subject>Tumors</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90FFLwzAQB_AgipvTFz-A5MUXoTNJ07R9lKJOGAqi4FtJrwmLtk1J6mTf3myd-iYchIPf3ZE_QueUzCkh7Bo6cHMmeMYO0JSSPI0I5ewQTQkhWZTw-G2CTrx_D23KkvgYTRgjgSXpFKmFkgP2KwsfWEsYrMMU9862dlAem24tvbEdll2NWzVIH8p4bDVeqV4OFlTTfDbSYZAOTGdbGWbw2gzO7mZ2zdqeoiMtG6_O9u8Mvd7dvhSLaPl0_1DcLCPggrBIyYoDrSsQKslErXOVKgpZ-EFdZxCzKucZqQVAKijXXOeVSjSL05yqmFNJ4xm6GveCs947pcvemVa6TUlJuc2q3GZV7rIK-GLE_WfVqvqX_oQTwOUeSA-y0U52YPyfS4RIaJIFR0f3ZRq1-edkWTwWz-Pxb7K2gtc</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Fang, Feng</creator><creator>Chang, Ruimin</creator><creator>Yang, Lianyue</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</general><scope>IQODW</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></search><sort><creationdate>20120401</creationdate><title>Heat shock factor 1 promotes invasion and metastasis of hepatocellular carcinoma in vitro and in vivo</title><author>Fang, Feng ; Chang, Ruimin ; Yang, Lianyue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4602-eab4c1dbc6e586df9e7e1c8543dd8c32b9480d6cc7614f4f9be5f23791e341a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - secondary</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>heat shock factor 1</topic><topic>heat shock protein 27</topic><topic>Heat Shock Transcription Factors</topic><topic>hepatocellular carcinoma</topic><topic>Humans</topic><topic>invasion</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Transplantation</topic><topic>Prognosis</topic><topic>Transcription Factors - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fang, Feng</creatorcontrib><creatorcontrib>Chang, Ruimin</creatorcontrib><creatorcontrib>Yang, Lianyue</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fang, Feng</au><au>Chang, Ruimin</au><au>Yang, Lianyue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heat shock factor 1 promotes invasion and metastasis of hepatocellular carcinoma in vitro and in vivo</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>118</volume><issue>7</issue><spage>1782</spage><epage>1794</epage><pages>1782-1794</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><coden>CANCAR</coden><abstract>BACKGROUND: Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in hepatocellular carcinoma (HCC) remain unknown. METHODS: Quantitative reverse transcriptase‐polymerase chain reaction analysis, Western blot analysis, and immunohistochemical staining were used to detect expression levels of HSF1, and its correlation with clinicopathologic parameters and the prognosis for patients with HCC were analyzed. In addition, the biologic function and molecular mechanisms of HSF1 in HCC were investigated in vitro and in vivo. RESULTS: HSF1 levels were elevated predominantly in HCC, especially in venous emboli from HCC (P &lt; .05), and high expression levels of HSF1 were correlated significantly with multiple nodules, venous invasion, absence of capsular formation, and high Edmondson‐Steiner grade as well as poor overall survival and disease‐free survival in patients with HCC (P &lt; .05). Multivariate Cox regression analysis revealed that high HSF1 expression was an independent prognostic factor for overall survival in patients with HCC (relative risk, 4.874; P &lt; .001). Finally, HSF1 was capable of promoting HCC cell migration and invasion in vitro and in vivo by facilitating the expression and phosphorylation of heat shock protein 27. CONCLUSIONS: Collectively, the current findings suggested that HSF1 may serve as a novel prognostic marker and therapeutic target for HCC. Cancer 2012;. © 2011 American Cancer Society. Heat shock factor 1 (HSF1) is elevated predominantly in hepatocellular carcinoma (HCC) and is significantly correlated with metastatic potential and with the prognosis of patients with HCC after hepatic resection. 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subjects Adolescent
Adult
Aged
Animals
Biological and medical sciences
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Carcinoma, Hepatocellular - secondary
DNA-Binding Proteins - metabolism
Female
Gastroenterology. Liver. Pancreas. Abdomen
heat shock factor 1
heat shock protein 27
Heat Shock Transcription Factors
hepatocellular carcinoma
Humans
invasion
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
metastasis
Mice
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Neoplasm Transplantation
Prognosis
Transcription Factors - metabolism
Tumors
title Heat shock factor 1 promotes invasion and metastasis of hepatocellular carcinoma in vitro and in vivo
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