Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis
Background. Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key gen...
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| Veröffentlicht in: | Canadian Journal of Gastroenterology and Hepatology 2022, Vol.2022, p.8996203-15 |
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| creator | Peng, Hong Ye, Ting Deng, Lei Yang, Xiaofang Jiang, Zheng Guo, Jinjun |
| description | Background. Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key genes involved in the action of activin and HGF in CRC were identified. Methods. HCT116 CRC cells were sequentially treated with activin and HGF and examined for migration and invasion in vitro and liver metastasis in vivo. RNA sequencing was performed to identify differentially expressed genes in response to activin and HGF. Results. Sequential treatment with activin and HGF-enhanced CRC cell migration, invasion, and metastasis. CXCR4 and AFP expressions were increased by activin and HGF treatment. Knockdown of FOXM1 blocked liver metastasis from HCT116 cells pretreated with activin and HGF and suppressed CXCR4 and AFP expression. Activin alone increased the mRNA and protein expression of FOXM1. In contrast, HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. SMAD2 was required for activin-mediated FOXM1 induction. FOXM1 transactivated CXCR4 by directly binding to the promoter of CXCR4. Additionally, CXCR4 regulated AFP expression through the NF-κB pathway. Conclusions. Sequential treatment with activin and HGF accelerates CRC invasion and liver metastasis, which involves the upregulation and activation of FOXM1 and induction of CXCR4 and AFP. |
| doi_str_mv | 10.1155/2022/8996203 |
| format | Article |
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Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key genes involved in the action of activin and HGF in CRC were identified. Methods. HCT116 CRC cells were sequentially treated with activin and HGF and examined for migration and invasion in vitro and liver metastasis in vivo. RNA sequencing was performed to identify differentially expressed genes in response to activin and HGF. Results. Sequential treatment with activin and HGF-enhanced CRC cell migration, invasion, and metastasis. CXCR4 and AFP expressions were increased by activin and HGF treatment. Knockdown of FOXM1 blocked liver metastasis from HCT116 cells pretreated with activin and HGF and suppressed CXCR4 and AFP expression. Activin alone increased the mRNA and protein expression of FOXM1. In contrast, HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. SMAD2 was required for activin-mediated FOXM1 induction. FOXM1 transactivated CXCR4 by directly binding to the promoter of CXCR4. Additionally, CXCR4 regulated AFP expression through the NF-κB pathway. Conclusions. Sequential treatment with activin and HGF accelerates CRC invasion and liver metastasis, which involves the upregulation and activation of FOXM1 and induction of CXCR4 and AFP.</description><identifier>ISSN: 2291-2789</identifier><identifier>EISSN: 2291-2797</identifier><identifier>DOI: 10.1155/2022/8996203</identifier><identifier>PMID: 36591565</identifier><language>eng</language><publisher>Egypt: Hindawi</publisher><subject>Activins - pharmacology ; alpha-Fetoproteins - metabolism ; Cancer therapies ; Cell culture ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Forkhead Box Protein M1 - genetics ; Forkhead Box Protein M1 - metabolism ; Gene expression ; Growth factors ; Hepatocyte Growth Factor - pharmacology ; Humans ; Laboratory animals ; Liver ; Liver Neoplasms - drug therapy ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - secondary ; Metastasis ; Plasmids ; Proteins ; Stem cells ; Up-Regulation ; Wound healing</subject><ispartof>Canadian Journal of Gastroenterology and Hepatology, 2022, Vol.2022, p.8996203-15</ispartof><rights>Copyright © 2022 Hong Peng et al.</rights><rights>Copyright © 2022 Hong Peng et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2022 Hong Peng et al. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-a6827a1680bc0f40fbc11383906e2c51f0c77b921f9834540c3761564a6f0fa83</citedby><cites>FETCH-LOGICAL-c514t-a6827a1680bc0f40fbc11383906e2c51f0c77b921f9834540c3761564a6f0fa83</cites><orcidid>0000-0001-5583-5484 ; 0000-0002-6242-4314 ; 0000-0002-1027-0309 ; 0000-0002-5265-0561 ; 0000-0002-6886-8370</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/PMC9803576/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803576/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,877,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36591565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ying, Hou-Qun</contributor><contributor>Hou-Qun Ying</contributor><creatorcontrib>Peng, Hong</creatorcontrib><creatorcontrib>Ye, Ting</creatorcontrib><creatorcontrib>Deng, Lei</creatorcontrib><creatorcontrib>Yang, Xiaofang</creatorcontrib><creatorcontrib>Jiang, Zheng</creatorcontrib><creatorcontrib>Guo, Jinjun</creatorcontrib><title>Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis</title><title>Canadian Journal of Gastroenterology and Hepatology</title><addtitle>Can J Gastroenterol Hepatol</addtitle><description>Background. Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key genes involved in the action of activin and HGF in CRC were identified. Methods. HCT116 CRC cells were sequentially treated with activin and HGF and examined for migration and invasion in vitro and liver metastasis in vivo. RNA sequencing was performed to identify differentially expressed genes in response to activin and HGF. Results. Sequential treatment with activin and HGF-enhanced CRC cell migration, invasion, and metastasis. CXCR4 and AFP expressions were increased by activin and HGF treatment. Knockdown of FOXM1 blocked liver metastasis from HCT116 cells pretreated with activin and HGF and suppressed CXCR4 and AFP expression. Activin alone increased the mRNA and protein expression of FOXM1. In contrast, HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. SMAD2 was required for activin-mediated FOXM1 induction. FOXM1 transactivated CXCR4 by directly binding to the promoter of CXCR4. Additionally, CXCR4 regulated AFP expression through the NF-κB pathway. Conclusions. Sequential treatment with activin and HGF accelerates CRC invasion and liver metastasis, which involves the upregulation and activation of FOXM1 and induction of CXCR4 and AFP.</description><subject>Activins - pharmacology</subject><subject>alpha-Fetoproteins - metabolism</subject><subject>Cancer therapies</subject><subject>Cell culture</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Forkhead Box Protein M1 - genetics</subject><subject>Forkhead Box Protein M1 - metabolism</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Hepatocyte Growth Factor - pharmacology</subject><subject>Humans</subject><subject>Laboratory animals</subject><subject>Liver</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - secondary</subject><subject>Metastasis</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Stem cells</subject><subject>Up-Regulation</subject><subject>Wound healing</subject><issn>2291-2789</issn><issn>2291-2797</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp9kUtrGzEQgJfS0oQ0t56LoMfWyUhavS6FYOrE4JBCU-hNzGq1sYy9crWyTfrrq8SuaS4Fodd8fNLMVNV7CheUCnHJgLFLbYxkwF9Vp4wZOmLKqNfHvTYn1fkwLACAMiEMZ2-rEy6FoUKK0-r3d_9r4_sccEnuk8e8KgeyC3lOrlwO29AT7Fty49eYo3vMnlynuCvRCbocE5n27cb5gUzuft5SkiP5luIqFmwclzF5l4t3jL3ziczCtsy3PuNQRhjeVW86XA7-_LCeVT8mX-_HN6PZ3fV0fDUbOUHrPEKpmUIqNTQOuhq6xlHKNTcgPStIB06pxjDaGc1rUYPjSpbkapQddKj5WTXde9uIC7tOYYXp0UYM9vkipgeLKQe39FZ5ZK6twQDUNUfRgERojXLoWtSyKa4ve9d606x860qxEi5fSF9G-jC3D3FrjQYulCyCjwdBiqXwQ7aLuEl9yd8yJYxWwDUt1Oc95VIchuS74wsU7FPj7VPj7aHxBf_w76-O8N82F-DTHpiHvsVd-L_uD5nNtbY</recordid><startdate>2022</startdate><enddate>2022</enddate><creator>Peng, Hong</creator><creator>Ye, Ting</creator><creator>Deng, Lei</creator><creator>Yang, Xiaofang</creator><creator>Jiang, Zheng</creator><creator>Guo, Jinjun</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8FQ</scope><scope>8FV</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>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5583-5484</orcidid><orcidid>https://orcid.org/0000-0002-6242-4314</orcidid><orcidid>https://orcid.org/0000-0002-1027-0309</orcidid><orcidid>https://orcid.org/0000-0002-5265-0561</orcidid><orcidid>https://orcid.org/0000-0002-6886-8370</orcidid></search><sort><creationdate>2022</creationdate><title>Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis</title><author>Peng, Hong ; Ye, Ting ; Deng, Lei ; Yang, Xiaofang ; Jiang, Zheng ; Guo, Jinjun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-a6827a1680bc0f40fbc11383906e2c51f0c77b921f9834540c3761564a6f0fa83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Activins - pharmacology</topic><topic>alpha-Fetoproteins - metabolism</topic><topic>Cancer therapies</topic><topic>Cell culture</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Forkhead Box Protein M1 - genetics</topic><topic>Forkhead Box Protein M1 - metabolism</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Hepatocyte Growth Factor - pharmacology</topic><topic>Humans</topic><topic>Laboratory animals</topic><topic>Liver</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - secondary</topic><topic>Metastasis</topic><topic>Plasmids</topic><topic>Proteins</topic><topic>Stem cells</topic><topic>Up-Regulation</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peng, Hong</creatorcontrib><creatorcontrib>Ye, Ting</creatorcontrib><creatorcontrib>Deng, Lei</creatorcontrib><creatorcontrib>Yang, Xiaofang</creatorcontrib><creatorcontrib>Jiang, Zheng</creatorcontrib><creatorcontrib>Guo, Jinjun</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access Journals</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 Central (Corporate)</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>Canadian Business & Current Affairs Database</collection><collection>Canadian Business & Current Affairs Database (Alumni Edition)</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>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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Canadian Journal of Gastroenterology and Hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peng, Hong</au><au>Ye, Ting</au><au>Deng, Lei</au><au>Yang, Xiaofang</au><au>Jiang, Zheng</au><au>Guo, Jinjun</au><au>Ying, Hou-Qun</au><au>Hou-Qun Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis</atitle><jtitle>Canadian Journal of Gastroenterology and Hepatology</jtitle><addtitle>Can J Gastroenterol Hepatol</addtitle><date>2022</date><risdate>2022</risdate><volume>2022</volume><spage>8996203</spage><epage>15</epage><pages>8996203-15</pages><issn>2291-2789</issn><eissn>2291-2797</eissn><abstract>Background. Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key genes involved in the action of activin and HGF in CRC were identified. Methods. HCT116 CRC cells were sequentially treated with activin and HGF and examined for migration and invasion in vitro and liver metastasis in vivo. RNA sequencing was performed to identify differentially expressed genes in response to activin and HGF. Results. Sequential treatment with activin and HGF-enhanced CRC cell migration, invasion, and metastasis. CXCR4 and AFP expressions were increased by activin and HGF treatment. Knockdown of FOXM1 blocked liver metastasis from HCT116 cells pretreated with activin and HGF and suppressed CXCR4 and AFP expression. Activin alone increased the mRNA and protein expression of FOXM1. In contrast, HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. SMAD2 was required for activin-mediated FOXM1 induction. FOXM1 transactivated CXCR4 by directly binding to the promoter of CXCR4. Additionally, CXCR4 regulated AFP expression through the NF-κB pathway. Conclusions. Sequential treatment with activin and HGF accelerates CRC invasion and liver metastasis, which involves the upregulation and activation of FOXM1 and induction of CXCR4 and AFP.</abstract><cop>Egypt</cop><pub>Hindawi</pub><pmid>36591565</pmid><doi>10.1155/2022/8996203</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-5583-5484</orcidid><orcidid>https://orcid.org/0000-0002-6242-4314</orcidid><orcidid>https://orcid.org/0000-0002-1027-0309</orcidid><orcidid>https://orcid.org/0000-0002-5265-0561</orcidid><orcidid>https://orcid.org/0000-0002-6886-8370</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Activins - pharmacology alpha-Fetoproteins - metabolism Cancer therapies Cell culture Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Forkhead Box Protein M1 - genetics Forkhead Box Protein M1 - metabolism Gene expression Growth factors Hepatocyte Growth Factor - pharmacology Humans Laboratory animals Liver Liver Neoplasms - drug therapy Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - secondary Metastasis Plasmids Proteins Stem cells Up-Regulation Wound healing |
| title | Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis |
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