Gastric Inhibitory Polypeptide Receptor (GIPR) Overexpression Reduces the Tumorigenic Potential of Retinoblastoma Cells
Retinoblastoma (RB) is the most common malignant intraocular tumor in early childhood. Gene expression profiling revealed that the gastric inhibitory polypeptide receptor (GIPR) is upregulated following trefoil factor family peptide 1 (TFF1) overexpression in RB cells. In the study presented, we fou...
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| Veröffentlicht in: | Cancers 2024-05, Vol.16 (9), p.1656 |
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| creator | Haase, André Alefeld, Emily Yalinci, Fatma Meenen, Dario Van Busch, Maike Anna Dünker, Nicole |
| description | Retinoblastoma (RB) is the most common malignant intraocular tumor in early childhood. Gene expression profiling revealed that the gastric inhibitory polypeptide receptor (GIPR) is upregulated following trefoil factor family peptide 1 (TFF1) overexpression in RB cells. In the study presented, we found this G protein-coupled transmembrane receptor to be co-expressed with TFF1, a new diagnostic and prognostic RB biomarker for advanced subtype 2 RBs. Functional analyses in two RB cell lines revealed a significant reduction in cell viability and growth and a concomitant increase in apoptosis following stable, lentiviral GIPR overexpression, matching the effects seen after TFF1 overexpression. In chicken chorioallantoic membrane (CAM) assays, GIPR-overexpressing RB cells developed significantly smaller CAM tumors. The effect of GIPR overexpression in RB cells was reversed by the GIPR inhibitor MK0893. The administration of recombinant TFF1 did not augment GIPR overexpression effects, suggesting that GIPR does not serve as a TFF1 receptor. Investigations of potential GIPR up- and downstream mediators suggest the involvement of miR-542-5p and p53 in GIPR signaling. Our results indicate a tumor suppressor role of GIPR in RB, suggesting its pathway as a new potential target for future retinoblastoma therapy. |
| doi_str_mv | 10.3390/cancers16091656 |
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Gene expression profiling revealed that the gastric inhibitory polypeptide receptor (GIPR) is upregulated following trefoil factor family peptide 1 (TFF1) overexpression in RB cells. In the study presented, we found this G protein-coupled transmembrane receptor to be co-expressed with TFF1, a new diagnostic and prognostic RB biomarker for advanced subtype 2 RBs. Functional analyses in two RB cell lines revealed a significant reduction in cell viability and growth and a concomitant increase in apoptosis following stable, lentiviral GIPR overexpression, matching the effects seen after TFF1 overexpression. In chicken chorioallantoic membrane (CAM) assays, GIPR-overexpressing RB cells developed significantly smaller CAM tumors. The effect of GIPR overexpression in RB cells was reversed by the GIPR inhibitor MK0893. The administration of recombinant TFF1 did not augment GIPR overexpression effects, suggesting that GIPR does not serve as a TFF1 receptor. Investigations of potential GIPR up- and downstream mediators suggest the involvement of miR-542-5p and p53 in GIPR signaling. Our results indicate a tumor suppressor role of GIPR in RB, suggesting its pathway as a new potential target for future retinoblastoma therapy.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers16091656</identifier><identifier>PMID: 38730608</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adjuvant treatment ; Analysis ; Apoptosis ; Binding sites ; Biomarkers ; Cancer ; Cancer therapies ; Cell cycle ; Cell surface receptors ; Cell viability ; Chemotherapy ; Children ; Chorioallantoic membrane ; Enzymes ; G proteins ; Gene expression ; Genes ; Glucose ; Medical prognosis ; p53 Protein ; Peptides ; Polypeptides ; Proteins ; Retinoblastoma ; Trefoil factor ; Tumor proteins ; Tumor suppressor genes ; Tumors ; Vision disorders in children</subject><ispartof>Cancers, 2024-05, Vol.16 (9), p.1656</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c387t-d761cdb08385888cef5ac60e7742a44c2c560c0c8534d6da433d0ccee6c41e083</cites><orcidid>0000-0001-9651-031X ; 0000-0002-4529-1396 ; 0000-0003-0286-9765 ; 0000-0003-1273-0644</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38730608$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haase, André</creatorcontrib><creatorcontrib>Alefeld, Emily</creatorcontrib><creatorcontrib>Yalinci, Fatma</creatorcontrib><creatorcontrib>Meenen, Dario Van</creatorcontrib><creatorcontrib>Busch, Maike Anna</creatorcontrib><creatorcontrib>Dünker, Nicole</creatorcontrib><title>Gastric Inhibitory Polypeptide Receptor (GIPR) Overexpression Reduces the Tumorigenic Potential of Retinoblastoma Cells</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Retinoblastoma (RB) is the most common malignant intraocular tumor in early childhood. Gene expression profiling revealed that the gastric inhibitory polypeptide receptor (GIPR) is upregulated following trefoil factor family peptide 1 (TFF1) overexpression in RB cells. In the study presented, we found this G protein-coupled transmembrane receptor to be co-expressed with TFF1, a new diagnostic and prognostic RB biomarker for advanced subtype 2 RBs. Functional analyses in two RB cell lines revealed a significant reduction in cell viability and growth and a concomitant increase in apoptosis following stable, lentiviral GIPR overexpression, matching the effects seen after TFF1 overexpression. In chicken chorioallantoic membrane (CAM) assays, GIPR-overexpressing RB cells developed significantly smaller CAM tumors. The effect of GIPR overexpression in RB cells was reversed by the GIPR inhibitor MK0893. The administration of recombinant TFF1 did not augment GIPR overexpression effects, suggesting that GIPR does not serve as a TFF1 receptor. Investigations of potential GIPR up- and downstream mediators suggest the involvement of miR-542-5p and p53 in GIPR signaling. Our results indicate a tumor suppressor role of GIPR in RB, suggesting its pathway as a new potential target for future retinoblastoma therapy.</description><subject>Adjuvant treatment</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Binding sites</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell surface receptors</subject><subject>Cell viability</subject><subject>Chemotherapy</subject><subject>Children</subject><subject>Chorioallantoic membrane</subject><subject>Enzymes</subject><subject>G proteins</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Glucose</subject><subject>Medical prognosis</subject><subject>p53 Protein</subject><subject>Peptides</subject><subject>Polypeptides</subject><subject>Proteins</subject><subject>Retinoblastoma</subject><subject>Trefoil factor</subject><subject>Tumor proteins</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><subject>Vision disorders in children</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><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>eNptkc9PHCEcxSdNTTXWs7eGpBd7WIWBAeZoNu12ExM3Rs8T9st3FDMDU2Bs978vVvvLCAe-gc97vORV1TGjp5y39AyMB4yJSdoy2cg31UFNVb2QshVv_5n3q6OU7mlZnDMl1btqn2vFqaT6oPq-MilHB2Tt79zW5RB3ZBOG3YRTdhbJFUKZQiQnq_Xm6hO5fMCIP6aIKbngy7OdARPJd0iu5zFEd4u-uG1CRp-dGUjoC5SdD9uh_BRGQ5Y4DOl9tdebIeHR83lY3Xz5fL38uri4XK2X5xcLKBnzwirJwG6p5rrRWgP2jQFJUSlRGyGghkZSoKAbLqy0RnBuKQCiBMGwyA6rkyffKYZvM6bcjS5BSWA8hjl1nDa8VVJqWdCPL9D7MEdf0v2iGGtFLf5St2bAzvk-5Gjg0bQ7Vy1vpKKyLtTpK1TZFkcHwWPvyv1_grMnAcSQUsS-m6IbTdx1jHaPbXcv2i6KD89x5-2I9g__u1v-E-VHpfU</recordid><startdate>20240501</startdate><enddate>20240501</enddate><creator>Haase, André</creator><creator>Alefeld, Emily</creator><creator>Yalinci, Fatma</creator><creator>Meenen, Dario Van</creator><creator>Busch, Maike Anna</creator><creator>Dünker, Nicole</creator><general>MDPI AG</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9651-031X</orcidid><orcidid>https://orcid.org/0000-0002-4529-1396</orcidid><orcidid>https://orcid.org/0000-0003-0286-9765</orcidid><orcidid>https://orcid.org/0000-0003-1273-0644</orcidid></search><sort><creationdate>20240501</creationdate><title>Gastric Inhibitory Polypeptide Receptor (GIPR) Overexpression Reduces the Tumorigenic Potential of Retinoblastoma Cells</title><author>Haase, André ; Alefeld, Emily ; Yalinci, Fatma ; Meenen, Dario Van ; Busch, Maike Anna ; Dünker, Nicole</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-d761cdb08385888cef5ac60e7742a44c2c560c0c8534d6da433d0ccee6c41e083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adjuvant treatment</topic><topic>Analysis</topic><topic>Apoptosis</topic><topic>Binding sites</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell surface receptors</topic><topic>Cell viability</topic><topic>Chemotherapy</topic><topic>Children</topic><topic>Chorioallantoic membrane</topic><topic>Enzymes</topic><topic>G proteins</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Glucose</topic><topic>Medical prognosis</topic><topic>p53 Protein</topic><topic>Peptides</topic><topic>Polypeptides</topic><topic>Proteins</topic><topic>Retinoblastoma</topic><topic>Trefoil factor</topic><topic>Tumor proteins</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><topic>Vision disorders in children</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Haase, André</creatorcontrib><creatorcontrib>Alefeld, Emily</creatorcontrib><creatorcontrib>Yalinci, Fatma</creatorcontrib><creatorcontrib>Meenen, Dario Van</creatorcontrib><creatorcontrib>Busch, Maike Anna</creatorcontrib><creatorcontrib>Dünker, Nicole</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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>ProQuest One Community College</collection><collection>ProQuest Central Korea</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 Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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>MEDLINE - Academic</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haase, André</au><au>Alefeld, Emily</au><au>Yalinci, Fatma</au><au>Meenen, Dario Van</au><au>Busch, Maike Anna</au><au>Dünker, Nicole</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gastric Inhibitory Polypeptide Receptor (GIPR) Overexpression Reduces the Tumorigenic Potential of Retinoblastoma Cells</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2024-05-01</date><risdate>2024</risdate><volume>16</volume><issue>9</issue><spage>1656</spage><pages>1656-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Retinoblastoma (RB) is the most common malignant intraocular tumor in early childhood. Gene expression profiling revealed that the gastric inhibitory polypeptide receptor (GIPR) is upregulated following trefoil factor family peptide 1 (TFF1) overexpression in RB cells. In the study presented, we found this G protein-coupled transmembrane receptor to be co-expressed with TFF1, a new diagnostic and prognostic RB biomarker for advanced subtype 2 RBs. Functional analyses in two RB cell lines revealed a significant reduction in cell viability and growth and a concomitant increase in apoptosis following stable, lentiviral GIPR overexpression, matching the effects seen after TFF1 overexpression. In chicken chorioallantoic membrane (CAM) assays, GIPR-overexpressing RB cells developed significantly smaller CAM tumors. The effect of GIPR overexpression in RB cells was reversed by the GIPR inhibitor MK0893. The administration of recombinant TFF1 did not augment GIPR overexpression effects, suggesting that GIPR does not serve as a TFF1 receptor. Investigations of potential GIPR up- and downstream mediators suggest the involvement of miR-542-5p and p53 in GIPR signaling. Our results indicate a tumor suppressor role of GIPR in RB, suggesting its pathway as a new potential target for future retinoblastoma therapy.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38730608</pmid><doi>10.3390/cancers16091656</doi><orcidid>https://orcid.org/0000-0001-9651-031X</orcidid><orcidid>https://orcid.org/0000-0002-4529-1396</orcidid><orcidid>https://orcid.org/0000-0003-0286-9765</orcidid><orcidid>https://orcid.org/0000-0003-1273-0644</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adjuvant treatment Analysis Apoptosis Binding sites Biomarkers Cancer Cancer therapies Cell cycle Cell surface receptors Cell viability Chemotherapy Children Chorioallantoic membrane Enzymes G proteins Gene expression Genes Glucose Medical prognosis p53 Protein Peptides Polypeptides Proteins Retinoblastoma Trefoil factor Tumor proteins Tumor suppressor genes Tumors Vision disorders in children |
| title | Gastric Inhibitory Polypeptide Receptor (GIPR) Overexpression Reduces the Tumorigenic Potential of Retinoblastoma Cells |
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