Ascl1-induced Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in small-cell lung cancer and Wnt11 regulates small-cell lung cancer biology
The involvement of Wnt signaling in human lung cancer remains unclear. This study investigated the role of Wnt11 in neuroendocrine (NE) differentiation, cell proliferation, and epithelial-to-mesenchymal transition (EMT) in human small-cell lung cancer (SCLC). Immunohistochemical staining of resected...
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Veröffentlicht in: | Laboratory investigation 2019-11, Vol.99 (11), p.1622-1635 |
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creator | Tenjin, Yuki Kudoh, Shinji Kubota, Sho Yamada, Tatsuya Matsuo, Akira Sato, Younosuke Ichimura, Takaya Kohrogi, Hirotsugu Sashida, Goro Sakagami, Takuro Ito, Takaaki |
description | The involvement of Wnt signaling in human lung cancer remains unclear. This study investigated the role of Wnt11 in neuroendocrine (NE) differentiation, cell proliferation, and epithelial-to-mesenchymal transition (EMT) in human small-cell lung cancer (SCLC). Immunohistochemical staining of resected specimens showed that Wnt11 was expressed at higher levels in SCLCs than in non-SCLCs; 58.8% of SCLC, 5.2% of adenocarcinoma (ADC), and 23.5% of squamous cell carcinoma tissues stained positive for Wnt11. A positive relationship was observed between Achaete-scute complex homolog 1 (Ascl1) and Wnt11 expression in SCLC cell lines, and this was supported by transcriptome data from SCLC tissue. The expression of Wnt11 and some NE markers increased after the transfection of ASCL1 into the A549 ADC cell line. Knockdown of Ascl1 downregulated Wnt11 expression in SCLC cell lines. Ascl1 regulated Wnt11 expression via lysine H3K27 acetylation at the enhancer region of the WNT11 gene. Wnt11 controlled NE differentiation, cell proliferation, and E-cadherin expression under the regulation of Ascl1 in SCLC cell lines. The phosphorylation of AKT and p38 mitogen-activated protein kinase markedly increased after transfection of WNT11 into the SBC3 SCLC cell line, which suggests that Wnt11 promotes cell proliferation in SCLC cell lines. Ascl1 plays an important role in regulating the Wnt signaling pathway and is one of the driver molecules of Wnt11 in human SCLC. Ascl1 and Wnt11 may employ a cooperative mechanism to control the biology of SCLC. The present results indicate the therapeutic potential of targeting the Ascl1–Wnt11 signaling axis and support the clinical utility of Wnt11 as a biological marker in SCLC. |
doi_str_mv | 10.1038/s41374-019-0277-y |
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This study investigated the role of Wnt11 in neuroendocrine (NE) differentiation, cell proliferation, and epithelial-to-mesenchymal transition (EMT) in human small-cell lung cancer (SCLC). Immunohistochemical staining of resected specimens showed that Wnt11 was expressed at higher levels in SCLCs than in non-SCLCs; 58.8% of SCLC, 5.2% of adenocarcinoma (ADC), and 23.5% of squamous cell carcinoma tissues stained positive for Wnt11. A positive relationship was observed between Achaete-scute complex homolog 1 (Ascl1) and Wnt11 expression in SCLC cell lines, and this was supported by transcriptome data from SCLC tissue. The expression of Wnt11 and some NE markers increased after the transfection of ASCL1 into the A549 ADC cell line. Knockdown of Ascl1 downregulated Wnt11 expression in SCLC cell lines. Ascl1 regulated Wnt11 expression via lysine H3K27 acetylation at the enhancer region of the WNT11 gene. Wnt11 controlled NE differentiation, cell proliferation, and E-cadherin expression under the regulation of Ascl1 in SCLC cell lines. The phosphorylation of AKT and p38 mitogen-activated protein kinase markedly increased after transfection of WNT11 into the SBC3 SCLC cell line, which suggests that Wnt11 promotes cell proliferation in SCLC cell lines. Ascl1 plays an important role in regulating the Wnt signaling pathway and is one of the driver molecules of Wnt11 in human SCLC. Ascl1 and Wnt11 may employ a cooperative mechanism to control the biology of SCLC. The present results indicate the therapeutic potential of targeting the Ascl1–Wnt11 signaling axis and support the clinical utility of Wnt11 as a biological marker in SCLC.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/s41374-019-0277-y</identifier><identifier>PMID: 31231131</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>13/51 ; 13/89 ; 38/1 ; 42/44 ; 45/77 ; 631/67/1612/2143 ; 631/67/395 ; 64/60 ; Acetylation ; Adenocarcinoma ; Adenocarcinoma of Lung - genetics ; Adenocarcinoma of Lung - metabolism ; Adenocarcinoma of Lung - pathology ; AKT protein ; Animals ; Antigens, CD - genetics ; Antigens, CD - metabolism ; ASCL1 protein ; Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biology ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biotechnology ; Cadherins - genetics ; Cadherins - metabolism ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Differentiation ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Cooperative control ; Differentiation ; Down-Regulation ; E-cadherin ; Enhancer Elements, Genetic ; Epithelial-Mesenchymal Transition ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Heterografts ; Histones - metabolism ; Homology ; Humans ; Imides - pharmacology ; Kinases ; Laboratory Medicine ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lysine ; Male ; MAP kinase ; Medicine ; Medicine & Public Health ; Mesenchyme ; Mice ; Mice, Knockout ; Neuroendocrine Cells - metabolism ; Neuroendocrine Cells - pathology ; Pathology ; Phosphorylation ; Protein kinase ; Quinolines - pharmacology ; RNA, Small Interfering - genetics ; Signal transduction ; Signaling ; Small cell lung carcinoma ; Small Cell Lung Carcinoma - genetics ; Small Cell Lung Carcinoma - metabolism ; Small Cell Lung Carcinoma - pathology ; Snail Family Transcription Factors - genetics ; Snail Family Transcription Factors - metabolism ; Squamous cell carcinoma ; Transfection ; Wnt protein ; Wnt Proteins - antagonists & inhibitors ; Wnt Proteins - genetics ; Wnt Proteins - metabolism ; Wnt Signaling Pathway - drug effects</subject><ispartof>Laboratory investigation, 2019-11, Vol.99 (11), p.1622-1635</ispartof><rights>2019 United States & Canadian Academy of Pathology</rights><rights>The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2019</rights><rights>Copyright Nature Publishing Group Nov 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-9d37ec6ebc598d3e6ea598c9af73c237a8b4817bc971ca08c6eedc5bc8185ff43</citedby><cites>FETCH-LOGICAL-c467t-9d37ec6ebc598d3e6ea598c9af73c237a8b4817bc971ca08c6eedc5bc8185ff43</cites><orcidid>0000-0003-2318-5987</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31231131$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tenjin, Yuki</creatorcontrib><creatorcontrib>Kudoh, Shinji</creatorcontrib><creatorcontrib>Kubota, Sho</creatorcontrib><creatorcontrib>Yamada, Tatsuya</creatorcontrib><creatorcontrib>Matsuo, Akira</creatorcontrib><creatorcontrib>Sato, Younosuke</creatorcontrib><creatorcontrib>Ichimura, Takaya</creatorcontrib><creatorcontrib>Kohrogi, Hirotsugu</creatorcontrib><creatorcontrib>Sashida, Goro</creatorcontrib><creatorcontrib>Sakagami, Takuro</creatorcontrib><creatorcontrib>Ito, Takaaki</creatorcontrib><title>Ascl1-induced Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in small-cell lung cancer and Wnt11 regulates small-cell lung cancer biology</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>The involvement of Wnt signaling in human lung cancer remains unclear. This study investigated the role of Wnt11 in neuroendocrine (NE) differentiation, cell proliferation, and epithelial-to-mesenchymal transition (EMT) in human small-cell lung cancer (SCLC). Immunohistochemical staining of resected specimens showed that Wnt11 was expressed at higher levels in SCLCs than in non-SCLCs; 58.8% of SCLC, 5.2% of adenocarcinoma (ADC), and 23.5% of squamous cell carcinoma tissues stained positive for Wnt11. A positive relationship was observed between Achaete-scute complex homolog 1 (Ascl1) and Wnt11 expression in SCLC cell lines, and this was supported by transcriptome data from SCLC tissue. The expression of Wnt11 and some NE markers increased after the transfection of ASCL1 into the A549 ADC cell line. Knockdown of Ascl1 downregulated Wnt11 expression in SCLC cell lines. Ascl1 regulated Wnt11 expression via lysine H3K27 acetylation at the enhancer region of the WNT11 gene. Wnt11 controlled NE differentiation, cell proliferation, and E-cadherin expression under the regulation of Ascl1 in SCLC cell lines. The phosphorylation of AKT and p38 mitogen-activated protein kinase markedly increased after transfection of WNT11 into the SBC3 SCLC cell line, which suggests that Wnt11 promotes cell proliferation in SCLC cell lines. Ascl1 plays an important role in regulating the Wnt signaling pathway and is one of the driver molecules of Wnt11 in human SCLC. Ascl1 and Wnt11 may employ a cooperative mechanism to control the biology of SCLC. The present results indicate the therapeutic potential of targeting the Ascl1–Wnt11 signaling axis and support the clinical utility of Wnt11 as a biological marker in SCLC.</description><subject>13/51</subject><subject>13/89</subject><subject>38/1</subject><subject>42/44</subject><subject>45/77</subject><subject>631/67/1612/2143</subject><subject>631/67/395</subject><subject>64/60</subject><subject>Acetylation</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma of Lung - genetics</subject><subject>Adenocarcinoma of Lung - metabolism</subject><subject>Adenocarcinoma of Lung - pathology</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - metabolism</subject><subject>ASCL1 protein</subject><subject>Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biotechnology</subject><subject>Cadherins - genetics</subject><subject>Cadherins - metabolism</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Differentiation</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cooperative control</subject><subject>Differentiation</subject><subject>Down-Regulation</subject><subject>E-cadherin</subject><subject>Enhancer Elements, Genetic</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Heterografts</subject><subject>Histones - metabolism</subject><subject>Homology</subject><subject>Humans</subject><subject>Imides - pharmacology</subject><subject>Kinases</subject><subject>Laboratory Medicine</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lysine</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neuroendocrine Cells - metabolism</subject><subject>Neuroendocrine Cells - pathology</subject><subject>Pathology</subject><subject>Phosphorylation</subject><subject>Protein kinase</subject><subject>Quinolines - pharmacology</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Small cell lung carcinoma</subject><subject>Small Cell Lung Carcinoma - 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genetics</topic><topic>Adenocarcinoma of Lung - metabolism</topic><topic>Adenocarcinoma of Lung - pathology</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - metabolism</topic><topic>ASCL1 protein</topic><topic>Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biotechnology</topic><topic>Cadherins - genetics</topic><topic>Cadherins - metabolism</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Differentiation</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cooperative control</topic><topic>Differentiation</topic><topic>Down-Regulation</topic><topic>E-cadherin</topic><topic>Enhancer Elements, Genetic</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Knockdown Techniques</topic><topic>Heterografts</topic><topic>Histones - metabolism</topic><topic>Homology</topic><topic>Humans</topic><topic>Imides - pharmacology</topic><topic>Kinases</topic><topic>Laboratory Medicine</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Lysine</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neuroendocrine Cells - metabolism</topic><topic>Neuroendocrine Cells - pathology</topic><topic>Pathology</topic><topic>Phosphorylation</topic><topic>Protein kinase</topic><topic>Quinolines - pharmacology</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Small cell lung carcinoma</topic><topic>Small Cell Lung Carcinoma - genetics</topic><topic>Small Cell Lung Carcinoma - metabolism</topic><topic>Small Cell Lung Carcinoma - pathology</topic><topic>Snail Family Transcription Factors - genetics</topic><topic>Snail Family Transcription Factors - metabolism</topic><topic>Squamous cell carcinoma</topic><topic>Transfection</topic><topic>Wnt protein</topic><topic>Wnt Proteins - antagonists & inhibitors</topic><topic>Wnt Proteins - genetics</topic><topic>Wnt Proteins - metabolism</topic><topic>Wnt Signaling Pathway - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tenjin, Yuki</creatorcontrib><creatorcontrib>Kudoh, Shinji</creatorcontrib><creatorcontrib>Kubota, Sho</creatorcontrib><creatorcontrib>Yamada, Tatsuya</creatorcontrib><creatorcontrib>Matsuo, Akira</creatorcontrib><creatorcontrib>Sato, Younosuke</creatorcontrib><creatorcontrib>Ichimura, Takaya</creatorcontrib><creatorcontrib>Kohrogi, Hirotsugu</creatorcontrib><creatorcontrib>Sashida, Goro</creatorcontrib><creatorcontrib>Sakagami, Takuro</creatorcontrib><creatorcontrib>Ito, Takaaki</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect: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 Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tenjin, Yuki</au><au>Kudoh, Shinji</au><au>Kubota, Sho</au><au>Yamada, Tatsuya</au><au>Matsuo, Akira</au><au>Sato, Younosuke</au><au>Ichimura, Takaya</au><au>Kohrogi, Hirotsugu</au><au>Sashida, Goro</au><au>Sakagami, Takuro</au><au>Ito, Takaaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ascl1-induced Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in small-cell lung cancer and Wnt11 regulates small-cell lung cancer biology</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2019-11-01</date><risdate>2019</risdate><volume>99</volume><issue>11</issue><spage>1622</spage><epage>1635</epage><pages>1622-1635</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><abstract>The involvement of Wnt signaling in human lung cancer remains unclear. This study investigated the role of Wnt11 in neuroendocrine (NE) differentiation, cell proliferation, and epithelial-to-mesenchymal transition (EMT) in human small-cell lung cancer (SCLC). Immunohistochemical staining of resected specimens showed that Wnt11 was expressed at higher levels in SCLCs than in non-SCLCs; 58.8% of SCLC, 5.2% of adenocarcinoma (ADC), and 23.5% of squamous cell carcinoma tissues stained positive for Wnt11. A positive relationship was observed between Achaete-scute complex homolog 1 (Ascl1) and Wnt11 expression in SCLC cell lines, and this was supported by transcriptome data from SCLC tissue. The expression of Wnt11 and some NE markers increased after the transfection of ASCL1 into the A549 ADC cell line. Knockdown of Ascl1 downregulated Wnt11 expression in SCLC cell lines. Ascl1 regulated Wnt11 expression via lysine H3K27 acetylation at the enhancer region of the WNT11 gene. Wnt11 controlled NE differentiation, cell proliferation, and E-cadherin expression under the regulation of Ascl1 in SCLC cell lines. The phosphorylation of AKT and p38 mitogen-activated protein kinase markedly increased after transfection of WNT11 into the SBC3 SCLC cell line, which suggests that Wnt11 promotes cell proliferation in SCLC cell lines. Ascl1 plays an important role in regulating the Wnt signaling pathway and is one of the driver molecules of Wnt11 in human SCLC. Ascl1 and Wnt11 may employ a cooperative mechanism to control the biology of SCLC. The present results indicate the therapeutic potential of targeting the Ascl1–Wnt11 signaling axis and support the clinical utility of Wnt11 as a biological marker in SCLC.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>31231131</pmid><doi>10.1038/s41374-019-0277-y</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-2318-5987</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0023-6837 |
ispartof | Laboratory investigation, 2019-11, Vol.99 (11), p.1622-1635 |
issn | 0023-6837 1530-0307 |
language | eng |
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subjects | 13/51 13/89 38/1 42/44 45/77 631/67/1612/2143 631/67/395 64/60 Acetylation Adenocarcinoma Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - metabolism Adenocarcinoma of Lung - pathology AKT protein Animals Antigens, CD - genetics Antigens, CD - metabolism ASCL1 protein Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Biology Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Biotechnology Cadherins - genetics Cadherins - metabolism Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell Differentiation Cell growth Cell Line, Tumor Cell Proliferation Cooperative control Differentiation Down-Regulation E-cadherin Enhancer Elements, Genetic Epithelial-Mesenchymal Transition Gene expression Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Heterografts Histones - metabolism Homology Humans Imides - pharmacology Kinases Laboratory Medicine Lung cancer Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Lysine Male MAP kinase Medicine Medicine & Public Health Mesenchyme Mice Mice, Knockout Neuroendocrine Cells - metabolism Neuroendocrine Cells - pathology Pathology Phosphorylation Protein kinase Quinolines - pharmacology RNA, Small Interfering - genetics Signal transduction Signaling Small cell lung carcinoma Small Cell Lung Carcinoma - genetics Small Cell Lung Carcinoma - metabolism Small Cell Lung Carcinoma - pathology Snail Family Transcription Factors - genetics Snail Family Transcription Factors - metabolism Squamous cell carcinoma Transfection Wnt protein Wnt Proteins - antagonists & inhibitors Wnt Proteins - genetics Wnt Proteins - metabolism Wnt Signaling Pathway - drug effects |
title | Ascl1-induced Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in small-cell lung cancer and Wnt11 regulates small-cell lung cancer biology |
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