Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β‐catenin/ZEB1 axis
Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular‐based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclea...
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| Veröffentlicht in: | Cancer science 2021-09, Vol.112 (9), p.3732-3743 |
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| creator | Lee, Hyunjung Shim, Sehwan Kong, Joon Seog Kim, Min‐Jung Park, Sunhoo Lee, Seung‐Sook Kim, Areumnuri |
| description | Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular‐based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating β‐catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/β‐catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC.
We provided targeting the DRD2/β‐catenin/ZEB1 signaling axis as a potentially promising therapeutic strategy for patients with CRC. |
| doi_str_mv | 10.1111/cas.15026 |
| format | Article |
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We provided targeting the DRD2/β‐catenin/ZEB1 signaling axis as a potentially promising therapeutic strategy for patients with CRC.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.15026</identifier><identifier>PMID: 34118099</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject>Aged ; Animals ; beta Catenin - metabolism ; Cancer ; Care and treatment ; Cell Movement - genetics ; Cell Proliferation - drug effects ; Cell Proliferation - genetics ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Development and progression ; Disease Progression ; Dopamine Antagonists - pharmacology ; Dopamine receptors ; DRD2 ; Female ; HCT116 Cells ; Health aspects ; HT29 Cells ; Humans ; Life Sciences & Biomedicine ; Male ; metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Oncology ; Original ; Phenols ; pimozide ; Pimozide - pharmacology ; Receptors, Dopamine D2 - genetics ; Receptors, Dopamine D2 - metabolism ; RNA Interference ; Science & Technology ; Signal Transduction ; Survival Rate ; Transfection ; Tumor Burden - drug effects ; Tumor Burden - genetics ; Up-Regulation ; Xenograft Model Antitumor Assays ; ZEB1 ; Zinc Finger E-box-Binding Homeobox 1 - metabolism</subject><ispartof>Cancer science, 2021-09, Vol.112 (9), p.3732-3743</ispartof><rights>2021 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>COPYRIGHT 2021 John Wiley & Sons, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>14</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000669385500001</woscitedreferencesoriginalsourcerecordid><cites>FETCH-LOGICAL-g3976-7a85e1b1bbd36b88717484369892a2ef2468529bc6195a1f47b8a975fd050c483</cites><orcidid>0000-0002-3133-8974 ; 0000-0002-1111-9061</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/PMC8409418/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409418/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1418,2115,11567,27929,27930,39263,45579,45580,46057,46481,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34118099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Hyunjung</creatorcontrib><creatorcontrib>Shim, Sehwan</creatorcontrib><creatorcontrib>Kong, Joon Seog</creatorcontrib><creatorcontrib>Kim, Min‐Jung</creatorcontrib><creatorcontrib>Park, Sunhoo</creatorcontrib><creatorcontrib>Lee, Seung‐Sook</creatorcontrib><creatorcontrib>Kim, Areumnuri</creatorcontrib><title>Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β‐catenin/ZEB1 axis</title><title>Cancer science</title><addtitle>CANCER SCI</addtitle><addtitle>Cancer Sci</addtitle><description>Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular‐based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating β‐catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/β‐catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC.
We provided targeting the DRD2/β‐catenin/ZEB1 signaling axis as a potentially promising therapeutic strategy for patients with CRC.</description><subject>Aged</subject><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Proliferation - genetics</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Dopamine Antagonists - pharmacology</subject><subject>Dopamine receptors</subject><subject>DRD2</subject><subject>Female</subject><subject>HCT116 Cells</subject><subject>Health aspects</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Original</subject><subject>Phenols</subject><subject>pimozide</subject><subject>Pimozide - pharmacology</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>RNA Interference</subject><subject>Science & Technology</subject><subject>Signal Transduction</subject><subject>Survival Rate</subject><subject>Transfection</subject><subject>Tumor Burden - drug effects</subject><subject>Tumor Burden - genetics</subject><subject>Up-Regulation</subject><subject>Xenograft Model Antitumor Assays</subject><subject>ZEB1</subject><subject>Zinc Finger E-box-Binding Homeobox 1 - metabolism</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNkkuO1DAQhiMEYoaBBRdAltggoe6240fsDVJPMzykkWYBbNhYjlPpMUrsELub6R1H4CwchENwEtyPaTESC5yFS6nv_1VW_UXxlOApyWdmTZwSjktxrzgllKlJhbG4v6uricK0PCkexfgFYyqYYg-LE8oIkVip02J9tYYRboYRYnTBo9CiJgymdx7QCBaGFEb0ukTDGPqQICIbupAbyXTIGm9h3LaWt_J6g4xNbm2S80uUrgH9-vn7-w9rEnjnZ58vzgkyNy4-Lh60povw5HCfFZ_eXHxcvJtcXr19v5hfTpZUVWJSGcmB1KSuGypqKStSMcmoUFKVpoS2ZELyUtVWEMUNaVlVS6Mq3jaYY8skPSte7X2HVd1DY8Gn0XR6GF1vxo0Oxum7He-u9TKstWRYMbI1eHEwGMPXFcSkexctdJ3xEFZRl5xhTkrBcUaf79Gl6UA734bsaLe4nlcE58lFRTM1_QeVvwZ6Z4OH1uX_dwTP_n7CcfbbHWZA7oFvUIc2Wgd5LUcM5ygIRSXnucJk4VLeTfCLsPIpS1_-vzTTswOdR9wcMYL1NoU6p1DvUqgX8w-7gv4Bs07OhQ</recordid><startdate>202109</startdate><enddate>202109</enddate><creator>Lee, Hyunjung</creator><creator>Shim, Sehwan</creator><creator>Kong, Joon Seog</creator><creator>Kim, Min‐Jung</creator><creator>Park, Sunhoo</creator><creator>Lee, Seung‐Sook</creator><creator>Kim, Areumnuri</creator><general>Wiley</general><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3133-8974</orcidid><orcidid>https://orcid.org/0000-0002-1111-9061</orcidid></search><sort><creationdate>202109</creationdate><title>Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β‐catenin/ZEB1 axis</title><author>Lee, Hyunjung ; Shim, Sehwan ; Kong, Joon Seog ; Kim, Min‐Jung ; Park, Sunhoo ; Lee, Seung‐Sook ; Kim, Areumnuri</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g3976-7a85e1b1bbd36b88717484369892a2ef2468529bc6195a1f47b8a975fd050c483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Animals</topic><topic>beta Catenin - metabolism</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Proliferation - genetics</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>Dopamine Antagonists - pharmacology</topic><topic>Dopamine receptors</topic><topic>DRD2</topic><topic>Female</topic><topic>HCT116 Cells</topic><topic>Health aspects</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Original</topic><topic>Phenols</topic><topic>pimozide</topic><topic>Pimozide - pharmacology</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Dopamine D2 - metabolism</topic><topic>RNA Interference</topic><topic>Science & Technology</topic><topic>Signal Transduction</topic><topic>Survival Rate</topic><topic>Transfection</topic><topic>Tumor Burden - drug effects</topic><topic>Tumor Burden - genetics</topic><topic>Up-Regulation</topic><topic>Xenograft Model Antitumor Assays</topic><topic>ZEB1</topic><topic>Zinc Finger E-box-Binding Homeobox 1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Hyunjung</creatorcontrib><creatorcontrib>Shim, Sehwan</creatorcontrib><creatorcontrib>Kong, Joon Seog</creatorcontrib><creatorcontrib>Kim, Min‐Jung</creatorcontrib><creatorcontrib>Park, Sunhoo</creatorcontrib><creatorcontrib>Lee, Seung‐Sook</creatorcontrib><creatorcontrib>Kim, Areumnuri</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Hyunjung</au><au>Shim, Sehwan</au><au>Kong, Joon Seog</au><au>Kim, Min‐Jung</au><au>Park, Sunhoo</au><au>Lee, Seung‐Sook</au><au>Kim, Areumnuri</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β‐catenin/ZEB1 axis</atitle><jtitle>Cancer science</jtitle><stitle>CANCER SCI</stitle><addtitle>Cancer Sci</addtitle><date>2021-09</date><risdate>2021</risdate><volume>112</volume><issue>9</issue><spage>3732</spage><epage>3743</epage><pages>3732-3743</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular‐based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating β‐catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/β‐catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC.
We provided targeting the DRD2/β‐catenin/ZEB1 signaling axis as a potentially promising therapeutic strategy for patients with CRC.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>34118099</pmid><doi>10.1111/cas.15026</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3133-8974</orcidid><orcidid>https://orcid.org/0000-0002-1111-9061</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Animals beta Catenin - metabolism Cancer Care and treatment Cell Movement - genetics Cell Proliferation - drug effects Cell Proliferation - genetics Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Development and progression Disease Progression Dopamine Antagonists - pharmacology Dopamine receptors DRD2 Female HCT116 Cells Health aspects HT29 Cells Humans Life Sciences & Biomedicine Male metastasis Mice Mice, Inbred BALB C Mice, Nude Middle Aged Oncology Original Phenols pimozide Pimozide - pharmacology Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - metabolism RNA Interference Science & Technology Signal Transduction Survival Rate Transfection Tumor Burden - drug effects Tumor Burden - genetics Up-Regulation Xenograft Model Antitumor Assays ZEB1 Zinc Finger E-box-Binding Homeobox 1 - metabolism |
| title | Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β‐catenin/ZEB1 axis |
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