Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells
Although the Wnt/β-catenin pathway plays a central role in the carcinogenesis and maintenance of colorectal cancer (CRC), attempts to target the pathway itself have not been very successful. MyD88, an adaptor protein of the TLR/IL-1β signaling, has been implicated in the integrity of the intestines...
Gespeichert in:
Veröffentlicht in: | Oncogene 2021-01, Vol.40 (2), p.408-420 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 420 |
---|---|
container_issue | 2 |
container_start_page | 408 |
container_title | Oncogene |
container_volume | 40 |
creator | Kajino-Sakamoto, Rie Fujishita, Teruaki Taketo, Makoto Mark Aoki, Masahiro |
description | Although the Wnt/β-catenin pathway plays a central role in the carcinogenesis and maintenance of colorectal cancer (CRC), attempts to target the pathway itself have not been very successful. MyD88, an adaptor protein of the TLR/IL-1β signaling, has been implicated in the integrity of the intestines as well as in their tumorigenesis. In this study, we aimed to clarify the mechanisms by which epithelial MyD88 contributes to intestinal tumor formation and to address whether MyD88 can be a therapeutic target of CRC. Conditional knockout of
MyD88
in intestinal epithelial cells (IECs) reduced tumor formation in
Apc
+/Δ716
mice, accompanied by decreased proliferation and enhanced apoptosis of tumor epithelial cells. Mechanistically, the MyD88 loss caused inactivation of the JNK-mTORC1, NF-κB, and Wnt/β-catenin pathways in tumor cells. Induction of
MyD88
knockout in the intestinal tumor-derived organoids, but not in the normal IEC-derived organoids, induced apoptosis and reduced their growth. Treatment with the MyD88 inhibitor ST2825 also suppressed the growth of the intestinal tumor-derived organoids. Knockdown of
MYD88
in human CRC cell lines with mutations in
APC
or
CTNNB1
induced apoptosis and reduced their proliferation as well. These results indicate that MyD88 loss is synthetic lethal with mutational activation of the Wnt/β-catenin signaling in intestinal tumor epithelial cells. Inhibition of MyD88 signaling can thus be a novel therapeutic strategy for familial adenomatous polyposis (FAP) as well as for colorectal cancer harboring mutations in the Wnt/β-catenin signaling. |
doi_str_mv | 10.1038/s41388-020-01541-3 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2477821700</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2477821700</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-dba90d2120ab20400bb119b171eee061d3fb2c837313761cbdcc91ab9bd1effb3</originalsourceid><addsrcrecordid>eNp9kMFuFDEMhiMEokvhBThUkTiH2snMZuZYFVqQinpoK45RkvGwqWYz20lG1bwWD8IzNWVLufVk2f792_4Y-4jwGUE1x6lC1TQCJAjAukKhXrEVVnot6rqtXrMVtDWIVip5wN6ldAsAugX5lh0ohVqvq2bF0tUS84Zy8HygvLFDyAt3lO-JIv-xfGkaPowpcRs7vp2zzWGMiYfIf8Z8_Oe38DZTLOnO5s29XR47IWZKOUQ78Dxvx4nTLpQVQygFT8OQ3rM3vR0SfXiKh-zm7Ov16TdxcXn-_fTkQnil6yw6Z1voJEqwTkIF4Bxi61AjEcEaO9U76RulFSq9Ru8671u0rnUdUt87dcg-7X1303g3l5vM7ThP5a5kZKV1I1EDFJXcq_xUHp2oN7spbO20GATzyNnsOZvC2fzlbFQZOnqynt2WuueRf2CLQO0FqbTiL5r-737B9gFKuYsq</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2477821700</pqid></control><display><type>article</type><title>Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Kajino-Sakamoto, Rie ; Fujishita, Teruaki ; Taketo, Makoto Mark ; Aoki, Masahiro</creator><creatorcontrib>Kajino-Sakamoto, Rie ; Fujishita, Teruaki ; Taketo, Makoto Mark ; Aoki, Masahiro</creatorcontrib><description>Although the Wnt/β-catenin pathway plays a central role in the carcinogenesis and maintenance of colorectal cancer (CRC), attempts to target the pathway itself have not been very successful. MyD88, an adaptor protein of the TLR/IL-1β signaling, has been implicated in the integrity of the intestines as well as in their tumorigenesis. In this study, we aimed to clarify the mechanisms by which epithelial MyD88 contributes to intestinal tumor formation and to address whether MyD88 can be a therapeutic target of CRC. Conditional knockout of
MyD88
in intestinal epithelial cells (IECs) reduced tumor formation in
Apc
+/Δ716
mice, accompanied by decreased proliferation and enhanced apoptosis of tumor epithelial cells. Mechanistically, the MyD88 loss caused inactivation of the JNK-mTORC1, NF-κB, and Wnt/β-catenin pathways in tumor cells. Induction of
MyD88
knockout in the intestinal tumor-derived organoids, but not in the normal IEC-derived organoids, induced apoptosis and reduced their growth. Treatment with the MyD88 inhibitor ST2825 also suppressed the growth of the intestinal tumor-derived organoids. Knockdown of
MYD88
in human CRC cell lines with mutations in
APC
or
CTNNB1
induced apoptosis and reduced their proliferation as well. These results indicate that MyD88 loss is synthetic lethal with mutational activation of the Wnt/β-catenin signaling in intestinal tumor epithelial cells. Inhibition of MyD88 signaling can thus be a novel therapeutic strategy for familial adenomatous polyposis (FAP) as well as for colorectal cancer harboring mutations in the Wnt/β-catenin signaling.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-020-01541-3</identifier><identifier>PMID: 33177648</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 13/109 ; 13/2 ; 13/51 ; 13/89 ; 13/95 ; 38/61 ; 631/208/68 ; 631/67/1504/1885 ; 64/60 ; Adenomatous polyposis coli ; Animals ; Apoptosis ; beta Catenin - genetics ; Carcinogenesis ; Cell Biology ; Cell Proliferation ; Cells, Cultured ; Colorectal cancer ; Colorectal carcinoma ; Epithelial cells ; Familial adenomatous polyposis ; Female ; Human Genetics ; IL-1β ; Internal Medicine ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - pathology ; Intestinal Neoplasms - genetics ; Intestinal Neoplasms - metabolism ; Intestinal Neoplasms - pathology ; Intestine ; Lethality ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; MyD88 protein ; Myeloid Differentiation Factor 88 - physiology ; NF-κB protein ; Oncology ; Organoids ; Signal transduction ; Synthetic Lethal Mutations ; Therapeutic targets ; Tumor cells ; Tumorigenesis ; Wnt protein ; Wnt Proteins - genetics ; β-Catenin</subject><ispartof>Oncogene, 2021-01, Vol.40 (2), p.408-420</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-dba90d2120ab20400bb119b171eee061d3fb2c837313761cbdcc91ab9bd1effb3</citedby><cites>FETCH-LOGICAL-c375t-dba90d2120ab20400bb119b171eee061d3fb2c837313761cbdcc91ab9bd1effb3</cites><orcidid>0000-0001-8194-2515 ; 0000-0003-4316-9490</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33177648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kajino-Sakamoto, Rie</creatorcontrib><creatorcontrib>Fujishita, Teruaki</creatorcontrib><creatorcontrib>Taketo, Makoto Mark</creatorcontrib><creatorcontrib>Aoki, Masahiro</creatorcontrib><title>Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Although the Wnt/β-catenin pathway plays a central role in the carcinogenesis and maintenance of colorectal cancer (CRC), attempts to target the pathway itself have not been very successful. MyD88, an adaptor protein of the TLR/IL-1β signaling, has been implicated in the integrity of the intestines as well as in their tumorigenesis. In this study, we aimed to clarify the mechanisms by which epithelial MyD88 contributes to intestinal tumor formation and to address whether MyD88 can be a therapeutic target of CRC. Conditional knockout of
MyD88
in intestinal epithelial cells (IECs) reduced tumor formation in
Apc
+/Δ716
mice, accompanied by decreased proliferation and enhanced apoptosis of tumor epithelial cells. Mechanistically, the MyD88 loss caused inactivation of the JNK-mTORC1, NF-κB, and Wnt/β-catenin pathways in tumor cells. Induction of
MyD88
knockout in the intestinal tumor-derived organoids, but not in the normal IEC-derived organoids, induced apoptosis and reduced their growth. Treatment with the MyD88 inhibitor ST2825 also suppressed the growth of the intestinal tumor-derived organoids. Knockdown of
MYD88
in human CRC cell lines with mutations in
APC
or
CTNNB1
induced apoptosis and reduced their proliferation as well. These results indicate that MyD88 loss is synthetic lethal with mutational activation of the Wnt/β-catenin signaling in intestinal tumor epithelial cells. Inhibition of MyD88 signaling can thus be a novel therapeutic strategy for familial adenomatous polyposis (FAP) as well as for colorectal cancer harboring mutations in the Wnt/β-catenin signaling.</description><subject>13/106</subject><subject>13/109</subject><subject>13/2</subject><subject>13/51</subject><subject>13/89</subject><subject>13/95</subject><subject>38/61</subject><subject>631/208/68</subject><subject>631/67/1504/1885</subject><subject>64/60</subject><subject>Adenomatous polyposis coli</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>beta Catenin - genetics</subject><subject>Carcinogenesis</subject><subject>Cell Biology</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Epithelial cells</subject><subject>Familial adenomatous polyposis</subject><subject>Female</subject><subject>Human Genetics</subject><subject>IL-1β</subject><subject>Internal Medicine</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - pathology</subject><subject>Intestinal Neoplasms - genetics</subject><subject>Intestinal Neoplasms - metabolism</subject><subject>Intestinal Neoplasms - pathology</subject><subject>Intestine</subject><subject>Lethality</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mutation</subject><subject>MyD88 protein</subject><subject>Myeloid Differentiation Factor 88 - physiology</subject><subject>NF-κB protein</subject><subject>Oncology</subject><subject>Organoids</subject><subject>Signal transduction</subject><subject>Synthetic Lethal Mutations</subject><subject>Therapeutic targets</subject><subject>Tumor cells</subject><subject>Tumorigenesis</subject><subject>Wnt protein</subject><subject>Wnt Proteins - genetics</subject><subject>β-Catenin</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kMFuFDEMhiMEokvhBThUkTiH2snMZuZYFVqQinpoK45RkvGwqWYz20lG1bwWD8IzNWVLufVk2f792_4Y-4jwGUE1x6lC1TQCJAjAukKhXrEVVnot6rqtXrMVtDWIVip5wN6ldAsAugX5lh0ohVqvq2bF0tUS84Zy8HygvLFDyAt3lO-JIv-xfGkaPowpcRs7vp2zzWGMiYfIf8Z8_Oe38DZTLOnO5s29XR47IWZKOUQ78Dxvx4nTLpQVQygFT8OQ3rM3vR0SfXiKh-zm7Ov16TdxcXn-_fTkQnil6yw6Z1voJEqwTkIF4Bxi61AjEcEaO9U76RulFSq9Ru8671u0rnUdUt87dcg-7X1303g3l5vM7ThP5a5kZKV1I1EDFJXcq_xUHp2oN7spbO20GATzyNnsOZvC2fzlbFQZOnqynt2WuueRf2CLQO0FqbTiL5r-737B9gFKuYsq</recordid><startdate>20210114</startdate><enddate>20210114</enddate><creator>Kajino-Sakamoto, Rie</creator><creator>Fujishita, Teruaki</creator><creator>Taketo, Makoto Mark</creator><creator>Aoki, Masahiro</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0001-8194-2515</orcidid><orcidid>https://orcid.org/0000-0003-4316-9490</orcidid></search><sort><creationdate>20210114</creationdate><title>Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells</title><author>Kajino-Sakamoto, Rie ; Fujishita, Teruaki ; Taketo, Makoto Mark ; Aoki, Masahiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-dba90d2120ab20400bb119b171eee061d3fb2c837313761cbdcc91ab9bd1effb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>13/106</topic><topic>13/109</topic><topic>13/2</topic><topic>13/51</topic><topic>13/89</topic><topic>13/95</topic><topic>38/61</topic><topic>631/208/68</topic><topic>631/67/1504/1885</topic><topic>64/60</topic><topic>Adenomatous polyposis coli</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>beta Catenin - genetics</topic><topic>Carcinogenesis</topic><topic>Cell Biology</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Epithelial cells</topic><topic>Familial adenomatous polyposis</topic><topic>Female</topic><topic>Human Genetics</topic><topic>IL-1β</topic><topic>Internal Medicine</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestinal Mucosa - pathology</topic><topic>Intestinal Neoplasms - genetics</topic><topic>Intestinal Neoplasms - metabolism</topic><topic>Intestinal Neoplasms - pathology</topic><topic>Intestine</topic><topic>Lethality</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mutation</topic><topic>MyD88 protein</topic><topic>Myeloid Differentiation Factor 88 - physiology</topic><topic>NF-κB protein</topic><topic>Oncology</topic><topic>Organoids</topic><topic>Signal transduction</topic><topic>Synthetic Lethal Mutations</topic><topic>Therapeutic targets</topic><topic>Tumor cells</topic><topic>Tumorigenesis</topic><topic>Wnt protein</topic><topic>Wnt Proteins - genetics</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kajino-Sakamoto, Rie</creatorcontrib><creatorcontrib>Fujishita, Teruaki</creatorcontrib><creatorcontrib>Taketo, Makoto Mark</creatorcontrib><creatorcontrib>Aoki, Masahiro</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>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest 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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest research library</collection><collection>ProQuest Biological Science Journals</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kajino-Sakamoto, Rie</au><au>Fujishita, Teruaki</au><au>Taketo, Makoto Mark</au><au>Aoki, Masahiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2021-01-14</date><risdate>2021</risdate><volume>40</volume><issue>2</issue><spage>408</spage><epage>420</epage><pages>408-420</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Although the Wnt/β-catenin pathway plays a central role in the carcinogenesis and maintenance of colorectal cancer (CRC), attempts to target the pathway itself have not been very successful. MyD88, an adaptor protein of the TLR/IL-1β signaling, has been implicated in the integrity of the intestines as well as in their tumorigenesis. In this study, we aimed to clarify the mechanisms by which epithelial MyD88 contributes to intestinal tumor formation and to address whether MyD88 can be a therapeutic target of CRC. Conditional knockout of
MyD88
in intestinal epithelial cells (IECs) reduced tumor formation in
Apc
+/Δ716
mice, accompanied by decreased proliferation and enhanced apoptosis of tumor epithelial cells. Mechanistically, the MyD88 loss caused inactivation of the JNK-mTORC1, NF-κB, and Wnt/β-catenin pathways in tumor cells. Induction of
MyD88
knockout in the intestinal tumor-derived organoids, but not in the normal IEC-derived organoids, induced apoptosis and reduced their growth. Treatment with the MyD88 inhibitor ST2825 also suppressed the growth of the intestinal tumor-derived organoids. Knockdown of
MYD88
in human CRC cell lines with mutations in
APC
or
CTNNB1
induced apoptosis and reduced their proliferation as well. These results indicate that MyD88 loss is synthetic lethal with mutational activation of the Wnt/β-catenin signaling in intestinal tumor epithelial cells. Inhibition of MyD88 signaling can thus be a novel therapeutic strategy for familial adenomatous polyposis (FAP) as well as for colorectal cancer harboring mutations in the Wnt/β-catenin signaling.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33177648</pmid><doi>10.1038/s41388-020-01541-3</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-8194-2515</orcidid><orcidid>https://orcid.org/0000-0003-4316-9490</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0950-9232 |
ispartof | Oncogene, 2021-01, Vol.40 (2), p.408-420 |
issn | 0950-9232 1476-5594 |
language | eng |
recordid | cdi_proquest_journals_2477821700 |
source | MEDLINE; Alma/SFX Local Collection |
subjects | 13/106 13/109 13/2 13/51 13/89 13/95 38/61 631/208/68 631/67/1504/1885 64/60 Adenomatous polyposis coli Animals Apoptosis beta Catenin - genetics Carcinogenesis Cell Biology Cell Proliferation Cells, Cultured Colorectal cancer Colorectal carcinoma Epithelial cells Familial adenomatous polyposis Female Human Genetics IL-1β Internal Medicine Intestinal Mucosa - metabolism Intestinal Mucosa - pathology Intestinal Neoplasms - genetics Intestinal Neoplasms - metabolism Intestinal Neoplasms - pathology Intestine Lethality Medicine Medicine & Public Health Mice Mice, Inbred C57BL Mice, Knockout Mutation MyD88 protein Myeloid Differentiation Factor 88 - physiology NF-κB protein Oncology Organoids Signal transduction Synthetic Lethal Mutations Therapeutic targets Tumor cells Tumorigenesis Wnt protein Wnt Proteins - genetics β-Catenin |
title | Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T08%3A14%3A11IST&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=Synthetic%20lethality%20between%20MyD88%20loss%20and%20mutations%20in%20Wnt/%CE%B2-catenin%20pathway%20in%20intestinal%20tumor%20epithelial%20cells&rft.jtitle=Oncogene&rft.au=Kajino-Sakamoto,%20Rie&rft.date=2021-01-14&rft.volume=40&rft.issue=2&rft.spage=408&rft.epage=420&rft.pages=408-420&rft.issn=0950-9232&rft.eissn=1476-5594&rft_id=info:doi/10.1038/s41388-020-01541-3&rft_dat=%3Cproquest_cross%3E2477821700%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=2477821700&rft_id=info:pmid/33177648&rfr_iscdi=true |