FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer
FAT1 regulates cell–cell adhesion, cell growth, cell migration, and actin dynamics as either oncogene or tumor suppressor in human cancers. We previously identified FAT1 was one of significant mutant genes in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanism o...
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| Veröffentlicht in: | Cancer letters 2017-07, Vol.397, p.83-93 |
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| creator | Hu, Xiaoling Zhai, Yuanfang Kong, Pengzhou Cui, Heyang Yan, Ting Yang, Jian Qian, Yu Ma, Yanchun Wang, Fang Li, Hongyi Cheng, Caixia Zhang, Ling Jia, Zhiwu Li, Yaoping Yang, Bin Xu, Enwei Wang, Juan Yang, Jie Bi, Yanghui Chang, Lu Wang, Yi Zhang, Yingchun Song, Bin Li, Guodong Shi, Ruyi Liu, Jing Zhang, Mingsheng Cheng, Xiaolong Cui, Yongping |
| description | FAT1 regulates cell–cell adhesion, cell growth, cell migration, and actin dynamics as either oncogene or tumor suppressor in human cancers. We previously identified FAT1 was one of significant mutant genes in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanism of FAT1 in ESCC have not been explored. In this study, we report that FAT1 expression was significantly lower in ESCC tumor tissues. Exogenous expression of FAT1 led to inhibition of cell proliferation and colony formation, as well as cell migration and invasion whereas FAT1 knockdown showed the opponent trends in vitro and in vivo. Moreover, FAT1 knockdown led to a statistically decrease of E-cadherin expression and a dramatically increase expression of N-cadherin, Vimentin, and Snail in a MAPK/ERK pathway-dependent manner. Meanwhile, over-expression of FAT1 resulted in the opposite trends. These alterations were abrogated in the presence of U0126, a MEK specific inhibitor. Collectively, our studies identified a novel role for FAT1 in inhibiting tumor growth and EMT occurrence in ESCC. We proposed that disruption of MAPK/ERK pathway by FAT1 contributes the EMT in ESCC and has important implications for understanding ESCC development.
•FAT1 is one of SMGs identified in ESCC via next-sequencing analyses.•Loss-of-function of FAT1 promotes cell growth and cell migration/invasion in ESCC.•FAT1 deregulates EMT in a MAPK pathway-dependent manner in ESCC. |
| doi_str_mv | 10.1016/j.canlet.2017.03.033 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1883841126</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S030438351730215X</els_id><sourcerecordid>1883841126</sourcerecordid><originalsourceid>FETCH-LOGICAL-c390t-171528a047558b458f37914f5a638aa15d09cc2137495f52e25d4928c198aa253</originalsourceid><addsrcrecordid>eNp9kUtrGzEUhUVpadyk_6AUQTfpYhw9R9KmYILThCQ0FHctFM0dW2ZekWYc_O8r47SLLAIXJNB3rs69B6EvlMwpoeXFdu5d18A4Z4SqOeG5-Ds0o1qxQhlN3qMZ4UQUXHN5gj6ltCWESKHkR3TCNC9LKdUMPV8tVhQPEXbQjQnDEMYNNME1uIUEnd_s23wfo-tSGEPf4fPl_eo73gWH7xcPtxfL37c4hXXnmtCt8eDGzbPb49BhSP2wcWvI6vQ0ubafEvbQNDi79hDP0IfaNQk-v5yn6M_VcnV5Xdz9-nlzubgrPDdkLKiikmlHsm2pH4XUNVeGilq6kmvnqKyI8Z5RroSRtWTAZCUM056a_MwkP0Xnx75D7J8mSKNtQzr4cB1kS5ZqzbWglJUZ_fYK3fZTzJMdKMOUFtyITIkj5WOfUoTaDjG0Lu4tJfYQjN3aYzD2EIwlPBfPsq8vzafHFqr_on9JZODHEYC8jV2AaJMPOQCoQgQ_2qoPb__wF91DntA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1892784394</pqid></control><display><type>article</type><title>FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Hu, Xiaoling ; Zhai, Yuanfang ; Kong, Pengzhou ; Cui, Heyang ; Yan, Ting ; Yang, Jian ; Qian, Yu ; Ma, Yanchun ; Wang, Fang ; Li, Hongyi ; Cheng, Caixia ; Zhang, Ling ; Jia, Zhiwu ; Li, Yaoping ; Yang, Bin ; Xu, Enwei ; Wang, Juan ; Yang, Jie ; Bi, Yanghui ; Chang, Lu ; Wang, Yi ; Zhang, Yingchun ; Song, Bin ; Li, Guodong ; Shi, Ruyi ; Liu, Jing ; Zhang, Mingsheng ; Cheng, Xiaolong ; Cui, Yongping</creator><creatorcontrib>Hu, Xiaoling ; Zhai, Yuanfang ; Kong, Pengzhou ; Cui, Heyang ; Yan, Ting ; Yang, Jian ; Qian, Yu ; Ma, Yanchun ; Wang, Fang ; Li, Hongyi ; Cheng, Caixia ; Zhang, Ling ; Jia, Zhiwu ; Li, Yaoping ; Yang, Bin ; Xu, Enwei ; Wang, Juan ; Yang, Jie ; Bi, Yanghui ; Chang, Lu ; Wang, Yi ; Zhang, Yingchun ; Song, Bin ; Li, Guodong ; Shi, Ruyi ; Liu, Jing ; Zhang, Mingsheng ; Cheng, Xiaolong ; Cui, Yongping</creatorcontrib><description>FAT1 regulates cell–cell adhesion, cell growth, cell migration, and actin dynamics as either oncogene or tumor suppressor in human cancers. We previously identified FAT1 was one of significant mutant genes in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanism of FAT1 in ESCC have not been explored. In this study, we report that FAT1 expression was significantly lower in ESCC tumor tissues. Exogenous expression of FAT1 led to inhibition of cell proliferation and colony formation, as well as cell migration and invasion whereas FAT1 knockdown showed the opponent trends in vitro and in vivo. Moreover, FAT1 knockdown led to a statistically decrease of E-cadherin expression and a dramatically increase expression of N-cadherin, Vimentin, and Snail in a MAPK/ERK pathway-dependent manner. Meanwhile, over-expression of FAT1 resulted in the opposite trends. These alterations were abrogated in the presence of U0126, a MEK specific inhibitor. Collectively, our studies identified a novel role for FAT1 in inhibiting tumor growth and EMT occurrence in ESCC. We proposed that disruption of MAPK/ERK pathway by FAT1 contributes the EMT in ESCC and has important implications for understanding ESCC development.
•FAT1 is one of SMGs identified in ESCC via next-sequencing analyses.•Loss-of-function of FAT1 promotes cell growth and cell migration/invasion in ESCC.•FAT1 deregulates EMT in a MAPK pathway-dependent manner in ESCC.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2017.03.033</identifier><identifier>PMID: 28366557</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Animals ; Antigens, CD - genetics ; Antigens, CD - metabolism ; Breast cancer ; Cadherins - genetics ; Cadherins - metabolism ; Carcinoma, Squamous Cell - enzymology ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Cell adhesion ; Cell adhesion & migration ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cloning ; Disruption ; E-cadherin ; EMT ; Epidermal growth factor ; Epithelial-Mesenchymal Transition - drug effects ; ESCC ; Esophageal cancer ; Esophageal Neoplasms - enzymology ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - pathology ; Esophageal Squamous Cell Carcinoma ; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors ; Extracellular Signal-Regulated MAP Kinases - metabolism ; FAT1 ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kinases ; Laboratory animals ; Male ; MAP Kinase Signaling System - drug effects ; MAPK pathway ; Metabolic pathways ; Metastasis ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Oncogenes ; Plasmids ; Protein Kinase Inhibitors - pharmacology ; Proteins ; RNA Interference ; Signal transduction ; Snail Family Transcription Factors - genetics ; Snail Family Transcription Factors - metabolism ; Squamous cell carcinoma ; Time Factors ; Transfection ; Tumor Burden ; Tumor suppressor ; Tumorigenesis ; Tumors ; Vimentin - genetics ; Vimentin - metabolism</subject><ispartof>Cancer letters, 2017-07, Vol.397, p.83-93</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Limited Jul 1, 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-171528a047558b458f37914f5a638aa15d09cc2137495f52e25d4928c198aa253</citedby><cites>FETCH-LOGICAL-c390t-171528a047558b458f37914f5a638aa15d09cc2137495f52e25d4928c198aa253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S030438351730215X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28366557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Xiaoling</creatorcontrib><creatorcontrib>Zhai, Yuanfang</creatorcontrib><creatorcontrib>Kong, Pengzhou</creatorcontrib><creatorcontrib>Cui, Heyang</creatorcontrib><creatorcontrib>Yan, Ting</creatorcontrib><creatorcontrib>Yang, Jian</creatorcontrib><creatorcontrib>Qian, Yu</creatorcontrib><creatorcontrib>Ma, Yanchun</creatorcontrib><creatorcontrib>Wang, Fang</creatorcontrib><creatorcontrib>Li, Hongyi</creatorcontrib><creatorcontrib>Cheng, Caixia</creatorcontrib><creatorcontrib>Zhang, Ling</creatorcontrib><creatorcontrib>Jia, Zhiwu</creatorcontrib><creatorcontrib>Li, Yaoping</creatorcontrib><creatorcontrib>Yang, Bin</creatorcontrib><creatorcontrib>Xu, Enwei</creatorcontrib><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Yang, Jie</creatorcontrib><creatorcontrib>Bi, Yanghui</creatorcontrib><creatorcontrib>Chang, Lu</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Zhang, Yingchun</creatorcontrib><creatorcontrib>Song, Bin</creatorcontrib><creatorcontrib>Li, Guodong</creatorcontrib><creatorcontrib>Shi, Ruyi</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Zhang, Mingsheng</creatorcontrib><creatorcontrib>Cheng, Xiaolong</creatorcontrib><creatorcontrib>Cui, Yongping</creatorcontrib><title>FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>FAT1 regulates cell–cell adhesion, cell growth, cell migration, and actin dynamics as either oncogene or tumor suppressor in human cancers. We previously identified FAT1 was one of significant mutant genes in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanism of FAT1 in ESCC have not been explored. In this study, we report that FAT1 expression was significantly lower in ESCC tumor tissues. Exogenous expression of FAT1 led to inhibition of cell proliferation and colony formation, as well as cell migration and invasion whereas FAT1 knockdown showed the opponent trends in vitro and in vivo. Moreover, FAT1 knockdown led to a statistically decrease of E-cadherin expression and a dramatically increase expression of N-cadherin, Vimentin, and Snail in a MAPK/ERK pathway-dependent manner. Meanwhile, over-expression of FAT1 resulted in the opposite trends. These alterations were abrogated in the presence of U0126, a MEK specific inhibitor. Collectively, our studies identified a novel role for FAT1 in inhibiting tumor growth and EMT occurrence in ESCC. We proposed that disruption of MAPK/ERK pathway by FAT1 contributes the EMT in ESCC and has important implications for understanding ESCC development.
•FAT1 is one of SMGs identified in ESCC via next-sequencing analyses.•Loss-of-function of FAT1 promotes cell growth and cell migration/invasion in ESCC.•FAT1 deregulates EMT in a MAPK pathway-dependent manner in ESCC.</description><subject>Animals</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - metabolism</subject><subject>Breast cancer</subject><subject>Cadherins - genetics</subject><subject>Cadherins - metabolism</subject><subject>Carcinoma, Squamous Cell - enzymology</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cloning</subject><subject>Disruption</subject><subject>E-cadherin</subject><subject>EMT</subject><subject>Epidermal growth factor</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>ESCC</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - enzymology</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Esophageal Squamous Cell Carcinoma</subject><subject>Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>FAT1</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAPK pathway</subject><subject>Metabolic pathways</subject><subject>Metastasis</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Invasiveness</subject><subject>Oncogenes</subject><subject>Plasmids</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proteins</subject><subject>RNA Interference</subject><subject>Signal transduction</subject><subject>Snail Family Transcription Factors - genetics</subject><subject>Snail Family Transcription Factors - metabolism</subject><subject>Squamous cell carcinoma</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Tumor Burden</subject><subject>Tumor suppressor</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Vimentin - genetics</subject><subject>Vimentin - metabolism</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtrGzEUhUVpadyk_6AUQTfpYhw9R9KmYILThCQ0FHctFM0dW2ZekWYc_O8r47SLLAIXJNB3rs69B6EvlMwpoeXFdu5d18A4Z4SqOeG5-Ds0o1qxQhlN3qMZ4UQUXHN5gj6ltCWESKHkR3TCNC9LKdUMPV8tVhQPEXbQjQnDEMYNNME1uIUEnd_s23wfo-tSGEPf4fPl_eo73gWH7xcPtxfL37c4hXXnmtCt8eDGzbPb49BhSP2wcWvI6vQ0ubafEvbQNDi79hDP0IfaNQk-v5yn6M_VcnV5Xdz9-nlzubgrPDdkLKiikmlHsm2pH4XUNVeGilq6kmvnqKyI8Z5RroSRtWTAZCUM056a_MwkP0Xnx75D7J8mSKNtQzr4cB1kS5ZqzbWglJUZ_fYK3fZTzJMdKMOUFtyITIkj5WOfUoTaDjG0Lu4tJfYQjN3aYzD2EIwlPBfPsq8vzafHFqr_on9JZODHEYC8jV2AaJMPOQCoQgQ_2qoPb__wF91DntA</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Hu, Xiaoling</creator><creator>Zhai, Yuanfang</creator><creator>Kong, Pengzhou</creator><creator>Cui, Heyang</creator><creator>Yan, Ting</creator><creator>Yang, Jian</creator><creator>Qian, Yu</creator><creator>Ma, Yanchun</creator><creator>Wang, Fang</creator><creator>Li, Hongyi</creator><creator>Cheng, Caixia</creator><creator>Zhang, Ling</creator><creator>Jia, Zhiwu</creator><creator>Li, Yaoping</creator><creator>Yang, Bin</creator><creator>Xu, Enwei</creator><creator>Wang, Juan</creator><creator>Yang, Jie</creator><creator>Bi, Yanghui</creator><creator>Chang, Lu</creator><creator>Wang, Yi</creator><creator>Zhang, Yingchun</creator><creator>Song, Bin</creator><creator>Li, Guodong</creator><creator>Shi, Ruyi</creator><creator>Liu, Jing</creator><creator>Zhang, Mingsheng</creator><creator>Cheng, Xiaolong</creator><creator>Cui, Yongping</creator><general>Elsevier B.V</general><general>Elsevier Limited</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20170701</creationdate><title>FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer</title><author>Hu, Xiaoling ; Zhai, Yuanfang ; Kong, Pengzhou ; Cui, Heyang ; Yan, Ting ; Yang, Jian ; Qian, Yu ; Ma, Yanchun ; Wang, Fang ; Li, Hongyi ; Cheng, Caixia ; Zhang, Ling ; Jia, Zhiwu ; Li, Yaoping ; Yang, Bin ; Xu, Enwei ; Wang, Juan ; Yang, Jie ; Bi, Yanghui ; Chang, Lu ; Wang, Yi ; Zhang, Yingchun ; Song, Bin ; Li, Guodong ; Shi, Ruyi ; Liu, Jing ; Zhang, Mingsheng ; Cheng, Xiaolong ; Cui, Yongping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-171528a047558b458f37914f5a638aa15d09cc2137495f52e25d4928c198aa253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - metabolism</topic><topic>Breast cancer</topic><topic>Cadherins - genetics</topic><topic>Cadherins - metabolism</topic><topic>Carcinoma, Squamous Cell - enzymology</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cloning</topic><topic>Disruption</topic><topic>E-cadherin</topic><topic>EMT</topic><topic>Epidermal growth factor</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>ESCC</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - enzymology</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophageal Squamous Cell Carcinoma</topic><topic>Extracellular Signal-Regulated MAP Kinases - 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genetics</topic><topic>Vimentin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Xiaoling</creatorcontrib><creatorcontrib>Zhai, Yuanfang</creatorcontrib><creatorcontrib>Kong, Pengzhou</creatorcontrib><creatorcontrib>Cui, Heyang</creatorcontrib><creatorcontrib>Yan, Ting</creatorcontrib><creatorcontrib>Yang, Jian</creatorcontrib><creatorcontrib>Qian, Yu</creatorcontrib><creatorcontrib>Ma, Yanchun</creatorcontrib><creatorcontrib>Wang, Fang</creatorcontrib><creatorcontrib>Li, Hongyi</creatorcontrib><creatorcontrib>Cheng, Caixia</creatorcontrib><creatorcontrib>Zhang, Ling</creatorcontrib><creatorcontrib>Jia, Zhiwu</creatorcontrib><creatorcontrib>Li, Yaoping</creatorcontrib><creatorcontrib>Yang, Bin</creatorcontrib><creatorcontrib>Xu, Enwei</creatorcontrib><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Yang, Jie</creatorcontrib><creatorcontrib>Bi, Yanghui</creatorcontrib><creatorcontrib>Chang, Lu</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Zhang, Yingchun</creatorcontrib><creatorcontrib>Song, Bin</creatorcontrib><creatorcontrib>Li, Guodong</creatorcontrib><creatorcontrib>Shi, Ruyi</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Zhang, Mingsheng</creatorcontrib><creatorcontrib>Cheng, Xiaolong</creatorcontrib><creatorcontrib>Cui, Yongping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Xiaoling</au><au>Zhai, Yuanfang</au><au>Kong, Pengzhou</au><au>Cui, Heyang</au><au>Yan, Ting</au><au>Yang, Jian</au><au>Qian, Yu</au><au>Ma, Yanchun</au><au>Wang, Fang</au><au>Li, Hongyi</au><au>Cheng, Caixia</au><au>Zhang, Ling</au><au>Jia, Zhiwu</au><au>Li, Yaoping</au><au>Yang, Bin</au><au>Xu, Enwei</au><au>Wang, Juan</au><au>Yang, Jie</au><au>Bi, Yanghui</au><au>Chang, Lu</au><au>Wang, Yi</au><au>Zhang, Yingchun</au><au>Song, Bin</au><au>Li, Guodong</au><au>Shi, Ruyi</au><au>Liu, Jing</au><au>Zhang, Mingsheng</au><au>Cheng, Xiaolong</au><au>Cui, Yongping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2017-07-01</date><risdate>2017</risdate><volume>397</volume><spage>83</spage><epage>93</epage><pages>83-93</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>FAT1 regulates cell–cell adhesion, cell growth, cell migration, and actin dynamics as either oncogene or tumor suppressor in human cancers. We previously identified FAT1 was one of significant mutant genes in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanism of FAT1 in ESCC have not been explored. In this study, we report that FAT1 expression was significantly lower in ESCC tumor tissues. Exogenous expression of FAT1 led to inhibition of cell proliferation and colony formation, as well as cell migration and invasion whereas FAT1 knockdown showed the opponent trends in vitro and in vivo. Moreover, FAT1 knockdown led to a statistically decrease of E-cadherin expression and a dramatically increase expression of N-cadherin, Vimentin, and Snail in a MAPK/ERK pathway-dependent manner. Meanwhile, over-expression of FAT1 resulted in the opposite trends. These alterations were abrogated in the presence of U0126, a MEK specific inhibitor. Collectively, our studies identified a novel role for FAT1 in inhibiting tumor growth and EMT occurrence in ESCC. We proposed that disruption of MAPK/ERK pathway by FAT1 contributes the EMT in ESCC and has important implications for understanding ESCC development.
•FAT1 is one of SMGs identified in ESCC via next-sequencing analyses.•Loss-of-function of FAT1 promotes cell growth and cell migration/invasion in ESCC.•FAT1 deregulates EMT in a MAPK pathway-dependent manner in ESCC.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>28366557</pmid><doi>10.1016/j.canlet.2017.03.033</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0304-3835 |
| ispartof | Cancer letters, 2017-07, Vol.397, p.83-93 |
| issn | 0304-3835 1872-7980 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1883841126 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antigens, CD - genetics Antigens, CD - metabolism Breast cancer Cadherins - genetics Cadherins - metabolism Carcinoma, Squamous Cell - enzymology Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cell adhesion Cell adhesion & migration Cell cycle Cell growth Cell Line, Tumor Cell Movement Cell Proliferation Cloning Disruption E-cadherin EMT Epidermal growth factor Epithelial-Mesenchymal Transition - drug effects ESCC Esophageal cancer Esophageal Neoplasms - enzymology Esophageal Neoplasms - genetics Esophageal Neoplasms - pathology Esophageal Squamous Cell Carcinoma Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases - metabolism FAT1 Female Gene Expression Regulation, Neoplastic Humans Kinases Laboratory animals Male MAP Kinase Signaling System - drug effects MAPK pathway Metabolic pathways Metastasis Mice, Inbred BALB C Mice, Nude Middle Aged Mutation Neoplasm Invasiveness Oncogenes Plasmids Protein Kinase Inhibitors - pharmacology Proteins RNA Interference Signal transduction Snail Family Transcription Factors - genetics Snail Family Transcription Factors - metabolism Squamous cell carcinoma Time Factors Transfection Tumor Burden Tumor suppressor Tumorigenesis Tumors Vimentin - genetics Vimentin - metabolism |
| title | FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T06%3A01%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=FAT1%20prevents%20epithelial%20mesenchymal%20transition%20(EMT)%20via%20MAPK/ERK%20signaling%20pathway%20in%20esophageal%20squamous%20cell%20cancer&rft.jtitle=Cancer%20letters&rft.au=Hu,%20Xiaoling&rft.date=2017-07-01&rft.volume=397&rft.spage=83&rft.epage=93&rft.pages=83-93&rft.issn=0304-3835&rft.eissn=1872-7980&rft_id=info:doi/10.1016/j.canlet.2017.03.033&rft_dat=%3Cproquest_cross%3E1883841126%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1892784394&rft_id=info:pmid/28366557&rft_els_id=S030438351730215X&rfr_iscdi=true |