Pepsinogen C Interacts with IQGAP1 to Inhibit the Metastasis of Gastric Cancer Cells by Suppressing Rho-GTPase Pathway
This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo. The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-fo...
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| Veröffentlicht in: | Cancers 2024-05, Vol.16 (10), p.1796 |
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| creator | Ding, Hanxi Liu, Yingnan Lu, Xiaodong Liu, Aoran Xu, Qian Yuan, Yuan |
| description | This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo.
The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR.
PGC inhibited the proliferation, viability, epithelial-mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated.
PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion. |
| doi_str_mv | 10.3390/cancers16101796 |
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The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR.
PGC inhibited the proliferation, viability, epithelial-mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated.
PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers16101796</identifier><identifier>PMID: 38791874</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animal models ; Apoptosis ; Bioinformatics ; Biotechnology ; Cancer ; Cancer cells ; Cell adhesion & migration ; Cell culture ; Cell cycle ; Cell differentiation ; Cell migration ; Cell proliferation ; Cholecystokinin ; Development and progression ; Down-regulation ; Enzymes ; Ethylenediaminetetraacetic acid ; Flow cytometry ; Gastric cancer ; Gastric mucosa ; GTPase-activating protein ; Guanine nucleotide-binding protein ; Guanosine triphosphatases ; Health aspects ; Immunofluorescence ; Immunoprecipitation ; IQGAP1 protein ; Liquid chromatography ; Mass spectrometry ; Mass spectroscopy ; Metastases ; Metastasis ; Neomycin ; Pepsin ; Prevention ; Proteins ; Signal transduction ; Stem cells ; Stomach cancer ; Therapeutic targets ; Transmission electron microscopy ; Tumor suppressor genes ; Tumors ; Wound healing</subject><ispartof>Cancers, 2024-05, Vol.16 (10), p.1796</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-909c29dab1fb091400e5163181d98027de84c6a51bac2debf7efb3c04728919a3</cites><orcidid>0000-0002-0443-5605</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38791874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ding, Hanxi</creatorcontrib><creatorcontrib>Liu, Yingnan</creatorcontrib><creatorcontrib>Lu, Xiaodong</creatorcontrib><creatorcontrib>Liu, Aoran</creatorcontrib><creatorcontrib>Xu, Qian</creatorcontrib><creatorcontrib>Yuan, Yuan</creatorcontrib><title>Pepsinogen C Interacts with IQGAP1 to Inhibit the Metastasis of Gastric Cancer Cells by Suppressing Rho-GTPase Pathway</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo.
The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR.
PGC inhibited the proliferation, viability, epithelial-mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated.
PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion.</description><subject>Animal models</subject><subject>Apoptosis</subject><subject>Bioinformatics</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cancer cells</subject><subject>Cell adhesion & migration</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Cholecystokinin</subject><subject>Development and progression</subject><subject>Down-regulation</subject><subject>Enzymes</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Flow cytometry</subject><subject>Gastric cancer</subject><subject>Gastric mucosa</subject><subject>GTPase-activating protein</subject><subject>Guanine nucleotide-binding protein</subject><subject>Guanosine triphosphatases</subject><subject>Health aspects</subject><subject>Immunofluorescence</subject><subject>Immunoprecipitation</subject><subject>IQGAP1 protein</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Neomycin</subject><subject>Pepsin</subject><subject>Prevention</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Stem cells</subject><subject>Stomach cancer</subject><subject>Therapeutic targets</subject><subject>Transmission electron microscopy</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><subject>Wound healing</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>eNptkd1P5CAUxYlZo0Z99s2Q-LIvVShtgcdJsztOonH8em4ovZ1iZkoFumb-exm_NQsk9wZ-5-SEi9ARJaeMSXKmVa_BeVpQQrksttBeSniaFIXMfn3pd9Gh9w8kLsYoL_gO2mWCSyp4tof-zWHwprcL6HGJZ30Ap3Tw-MmEDs-up5M5xcHGh87UJuDQAb6EoHw8xmPb4mnsndG4fAmDS1guPa7X-HYcBgc-ei_wTWeT6d1cecBzFbontT5A261aejh8q_vo_u-fu_I8ubiazsrJRaJjxJBIInUqG1XTtiaSZoRATgtGBW2kIClvQGS6UDmtlU4bqFsObc00yXgqJJWK7aPfr76Ds48j-FCtjNcxo-rBjr5ipCBMMJ6RiJ78QB_s6PqYLlK5ZExkOf-kFmoJlelbG-KHbUyrCZc54zIVG-r0P1TcDayMtj20Jt5_E5y9CrSz3jtoq8GZlXLripJqM-zqx7Cj4vgt7livoPng30fLngHAE6OP</recordid><startdate>20240501</startdate><enddate>20240501</enddate><creator>Ding, Hanxi</creator><creator>Liu, Yingnan</creator><creator>Lu, Xiaodong</creator><creator>Liu, Aoran</creator><creator>Xu, Qian</creator><creator>Yuan, Yuan</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/0000-0002-0443-5605</orcidid></search><sort><creationdate>20240501</creationdate><title>Pepsinogen C Interacts with IQGAP1 to Inhibit the Metastasis of Gastric Cancer Cells by Suppressing Rho-GTPase Pathway</title><author>Ding, Hanxi ; Liu, Yingnan ; Lu, Xiaodong ; Liu, Aoran ; Xu, Qian ; Yuan, Yuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-909c29dab1fb091400e5163181d98027de84c6a51bac2debf7efb3c04728919a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animal models</topic><topic>Apoptosis</topic><topic>Bioinformatics</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cancer cells</topic><topic>Cell adhesion & migration</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cell differentiation</topic><topic>Cell migration</topic><topic>Cell proliferation</topic><topic>Cholecystokinin</topic><topic>Development and progression</topic><topic>Down-regulation</topic><topic>Enzymes</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Flow cytometry</topic><topic>Gastric cancer</topic><topic>Gastric mucosa</topic><topic>GTPase-activating protein</topic><topic>Guanine nucleotide-binding protein</topic><topic>Guanosine triphosphatases</topic><topic>Health aspects</topic><topic>Immunofluorescence</topic><topic>Immunoprecipitation</topic><topic>IQGAP1 protein</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Neomycin</topic><topic>Pepsin</topic><topic>Prevention</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>Stem cells</topic><topic>Stomach cancer</topic><topic>Therapeutic targets</topic><topic>Transmission electron microscopy</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ding, Hanxi</creatorcontrib><creatorcontrib>Liu, Yingnan</creatorcontrib><creatorcontrib>Lu, Xiaodong</creatorcontrib><creatorcontrib>Liu, Aoran</creatorcontrib><creatorcontrib>Xu, Qian</creatorcontrib><creatorcontrib>Yuan, Yuan</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>Ding, Hanxi</au><au>Liu, Yingnan</au><au>Lu, Xiaodong</au><au>Liu, Aoran</au><au>Xu, Qian</au><au>Yuan, Yuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pepsinogen C Interacts with IQGAP1 to Inhibit the Metastasis of Gastric Cancer Cells by Suppressing Rho-GTPase Pathway</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2024-05-01</date><risdate>2024</risdate><volume>16</volume><issue>10</issue><spage>1796</spage><pages>1796-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo.
The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR.
PGC inhibited the proliferation, viability, epithelial-mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated.
PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38791874</pmid><doi>10.3390/cancers16101796</doi><orcidid>https://orcid.org/0000-0002-0443-5605</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animal models Apoptosis Bioinformatics Biotechnology Cancer Cancer cells Cell adhesion & migration Cell culture Cell cycle Cell differentiation Cell migration Cell proliferation Cholecystokinin Development and progression Down-regulation Enzymes Ethylenediaminetetraacetic acid Flow cytometry Gastric cancer Gastric mucosa GTPase-activating protein Guanine nucleotide-binding protein Guanosine triphosphatases Health aspects Immunofluorescence Immunoprecipitation IQGAP1 protein Liquid chromatography Mass spectrometry Mass spectroscopy Metastases Metastasis Neomycin Pepsin Prevention Proteins Signal transduction Stem cells Stomach cancer Therapeutic targets Transmission electron microscopy Tumor suppressor genes Tumors Wound healing |
| title | Pepsinogen C Interacts with IQGAP1 to Inhibit the Metastasis of Gastric Cancer Cells by Suppressing Rho-GTPase Pathway |
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