The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program
Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts expr...
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| Veröffentlicht in: | Genes & development 2010-11, Vol.24 (21), p.2383-2388 |
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| creator | Cai, Jing Zhang, Nailing Zheng, Yonggang de Wilde, Roeland F Maitra, Anirban Pan, Duojia |
| description | Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program. |
| doi_str_mv | 10.1101/gad.1978810 |
| format | Article |
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Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.1978810</identifier><identifier>PMID: 21041407</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Adaptor Proteins, Signal Transducing - deficiency ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - physiology ; Animals ; Blotting, Western ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Colonic Polyps - chemically induced ; Colonic Polyps - genetics ; Colonic Polyps - physiopathology ; Dextran Sulfate ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Intestinal Mucosa - metabolism ; Intestines - pathology ; Intestines - physiopathology ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phosphoproteins - deficiency ; Phosphoproteins - genetics ; Phosphoproteins - physiology ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Regeneration - genetics ; Regeneration - physiology ; Research Communication ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction - genetics ; Signal Transduction - physiology</subject><ispartof>Genes & development, 2010-11, Vol.24 (21), p.2383-2388</ispartof><rights>Copyright © 2010 by Cold Spring Harbor Laboratory Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-cd95db71a855bcc1d821eba671cb8d1b1435d632990066bac2c5a85c43f649493</citedby><cites>FETCH-LOGICAL-c478t-cd95db71a855bcc1d821eba671cb8d1b1435d632990066bac2c5a85c43f649493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964748/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964748/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21041407$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Jing</creatorcontrib><creatorcontrib>Zhang, Nailing</creatorcontrib><creatorcontrib>Zheng, Yonggang</creatorcontrib><creatorcontrib>de Wilde, Roeland F</creatorcontrib><creatorcontrib>Maitra, Anirban</creatorcontrib><creatorcontrib>Pan, Duojia</creatorcontrib><title>The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. 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Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.</description><subject>Adaptor Proteins, Signal Transducing - deficiency</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - physiology</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Colonic Polyps - chemically induced</subject><subject>Colonic Polyps - genetics</subject><subject>Colonic Polyps - physiopathology</subject><subject>Dextran Sulfate</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestines - pathology</subject><subject>Intestines - physiopathology</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Phosphoproteins - deficiency</subject><subject>Phosphoproteins - genetics</subject><subject>Phosphoproteins - physiology</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Regeneration - genetics</subject><subject>Regeneration - physiology</subject><subject>Research Communication</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1LAzEQxYMotlZP3iU3D7Ka7GbzcRGkqBUKXuo5ZLPpNrJN1iRV-t8baS16mTnMb9684QFwidEtxgjfdaq9xYJxjtERGOOaiKImjB2DMeICFaKiYgTOYnxHCFFE6SkYlRgRTBAbA71YGTizw-BhtJ1TvXUdHFRafaktDCamYHWKMGXKO-0746yGg0_GJat66JdQOWhdyqTN23klIyaoZL2DQ_BdUOtzcLJUfTQX-z4Bb0-Pi-msmL8-v0wf5oUmjKdCt6JuG4YVr-tGa9zyEptGUYZ1w1vcYFLVLa1KIfIftFG61HVmNamWlAgiqgm43-kOm2ZtWp09BtXLIdi1ClvplZX_J86uZOc_ZSkoYYRngeu9QPAfm_ySXNuoTd8rZ_wmSp6pirFcJuBmR-rgYwxmebiCkfxJReZU5D6VTF_9NXZgf2OovgG-LItF</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Cai, Jing</creator><creator>Zhang, Nailing</creator><creator>Zheng, Yonggang</creator><creator>de Wilde, Roeland F</creator><creator>Maitra, Anirban</creator><creator>Pan, Duojia</creator><general>Cold Spring Harbor Laboratory Press</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>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20101101</creationdate><title>The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program</title><author>Cai, Jing ; 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Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>21041407</pmid><doi>10.1101/gad.1978810</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - deficiency Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - physiology Animals Blotting, Western Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Colonic Polyps - chemically induced Colonic Polyps - genetics Colonic Polyps - physiopathology Dextran Sulfate Drosophila Proteins - genetics Drosophila Proteins - metabolism Female Gene Expression Humans Immunohistochemistry Intestinal Mucosa - metabolism Intestines - pathology Intestines - physiopathology Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Phosphoproteins - deficiency Phosphoproteins - genetics Phosphoproteins - physiology Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Regeneration - genetics Regeneration - physiology Research Communication Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Signal Transduction - genetics Signal Transduction - physiology |
| title | The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program |
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