G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin
Ras-GTPase activating SH3 domain-binding protein 1 (G3BP1) is a multifunctional binding protein involved in the development of a variety of human cancers. However, the role of G3BP1 in breast cancer progression remains largely unknown. In this study, we report that G3BP1 is upregulated and correlate...
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| Veröffentlicht in: | Acta pharmacologica Sinica 2021-11, Vol.42 (11), p.1900-1912 |
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| container_issue | 11 |
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| container_title | Acta pharmacologica Sinica |
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| creator | Zhang, Cong-hui Liu, Hong Zhao, Wu-li Zhao, Wen-xia Zhou, Hui-min Shao, Rong-guang |
| description | Ras-GTPase activating SH3 domain-binding protein 1 (G3BP1) is a multifunctional binding protein involved in the development of a variety of human cancers. However, the role of G3BP1 in breast cancer progression remains largely unknown. In this study, we report that G3BP1 is upregulated and correlated with poor prognosis in breast cancer. Overexpression of G3BP1 promotes breast cancer cell proliferation by stimulating β-catenin signaling, which upregulates a number of proliferation-related genes. We further show that G3BP1 improves the stability of β-catenin by inhibiting its ubiquitin-proteasome degradation rather than affecting the transcription of β-catenin. Mechanistically, elevated G3BP1 interacts with and inactivates GSK-3β to suppress β-catenin phosphorylation and degradation. Disturbing the G3BP1-GSK-3β interaction accelerates the degradation of β-catenin, impairing the proliferative capacity of breast cancer cells. Our study demonstrates that the regulatory mechanism of the G3BP1/GSK-3β/β-catenin axis may be a potential therapeutic target for breast cancer. |
| doi_str_mv | 10.1038/s41401-020-00598-w |
| format | Article |
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However, the role of G3BP1 in breast cancer progression remains largely unknown. In this study, we report that G3BP1 is upregulated and correlated with poor prognosis in breast cancer. Overexpression of G3BP1 promotes breast cancer cell proliferation by stimulating β-catenin signaling, which upregulates a number of proliferation-related genes. We further show that G3BP1 improves the stability of β-catenin by inhibiting its ubiquitin-proteasome degradation rather than affecting the transcription of β-catenin. Mechanistically, elevated G3BP1 interacts with and inactivates GSK-3β to suppress β-catenin phosphorylation and degradation. Disturbing the G3BP1-GSK-3β interaction accelerates the degradation of β-catenin, impairing the proliferative capacity of breast cancer cells. Our study demonstrates that the regulatory mechanism of the G3BP1/GSK-3β/β-catenin axis may be a potential therapeutic target for breast cancer.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/s41401-020-00598-w</identifier><identifier>PMID: 33536604</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Animals ; beta Catenin - antagonists & inhibitors ; beta Catenin - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Breast cancer ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cell growth ; Cell Line, Tumor ; Cell proliferation ; Cell Proliferation - physiology ; Degradation ; DNA Helicases - biosynthesis ; Female ; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors ; Glycogen Synthase Kinase 3 beta - metabolism ; Humans ; Immunology ; Internal Medicine ; MCF-7 Cells ; Medical Microbiology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Pharmacology/Toxicology ; Phosphorylation ; Poly-ADP-Ribose Binding Proteins - biosynthesis ; Proteasomes ; RNA Helicases - biosynthesis ; RNA Recognition Motif Proteins - biosynthesis ; Transcription ; Ubiquitin ; Vaccine ; Xenograft Model Antitumor Assays - methods ; β-Catenin</subject><ispartof>Acta pharmacologica Sinica, 2021-11, Vol.42 (11), p.1900-1912</ispartof><rights>The Author(s), under exclusive licence to CPS and SIMM 2021</rights><rights>2021. The Author(s), under exclusive licence to CPS and SIMM.</rights><rights>The Author(s), under exclusive licence to CPS and SIMM 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-f5fd3e2f0922839320620ae28509074736e4627c206bbb7d0a2f368d908226a73</citedby><cites>FETCH-LOGICAL-c502t-f5fd3e2f0922839320620ae28509074736e4627c206bbb7d0a2f368d908226a73</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/PMC8563869/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563869/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33536604$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Cong-hui</creatorcontrib><creatorcontrib>Liu, Hong</creatorcontrib><creatorcontrib>Zhao, Wu-li</creatorcontrib><creatorcontrib>Zhao, Wen-xia</creatorcontrib><creatorcontrib>Zhou, Hui-min</creatorcontrib><creatorcontrib>Shao, Rong-guang</creatorcontrib><title>G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacol Sin</addtitle><description>Ras-GTPase activating SH3 domain-binding protein 1 (G3BP1) is a multifunctional binding protein involved in the development of a variety of human cancers. However, the role of G3BP1 in breast cancer progression remains largely unknown. In this study, we report that G3BP1 is upregulated and correlated with poor prognosis in breast cancer. Overexpression of G3BP1 promotes breast cancer cell proliferation by stimulating β-catenin signaling, which upregulates a number of proliferation-related genes. We further show that G3BP1 improves the stability of β-catenin by inhibiting its ubiquitin-proteasome degradation rather than affecting the transcription of β-catenin. Mechanistically, elevated G3BP1 interacts with and inactivates GSK-3β to suppress β-catenin phosphorylation and degradation. Disturbing the G3BP1-GSK-3β interaction accelerates the degradation of β-catenin, impairing the proliferative capacity of breast cancer cells. Our study demonstrates that the regulatory mechanism of the G3BP1/GSK-3β/β-catenin axis may be a potential therapeutic target for breast cancer.</description><subject>Animals</subject><subject>beta Catenin - antagonists & inhibitors</subject><subject>beta Catenin - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - physiology</subject><subject>Degradation</subject><subject>DNA Helicases - biosynthesis</subject><subject>Female</subject><subject>Glycogen Synthase Kinase 3 beta - antagonists & inhibitors</subject><subject>Glycogen Synthase Kinase 3 beta - metabolism</subject><subject>Humans</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>MCF-7 Cells</subject><subject>Medical Microbiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Pharmacology/Toxicology</subject><subject>Phosphorylation</subject><subject>Poly-ADP-Ribose Binding Proteins - biosynthesis</subject><subject>Proteasomes</subject><subject>RNA Helicases - biosynthesis</subject><subject>RNA Recognition Motif Proteins - biosynthesis</subject><subject>Transcription</subject><subject>Ubiquitin</subject><subject>Vaccine</subject><subject>Xenograft Model Antitumor Assays - methods</subject><subject>β-Catenin</subject><issn>1671-4083</issn><issn>1745-7254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFUctu1TAQjRCIlsIPsECW2LAxjJ9xNki0gguiEkjA2nIS58ZVYl9shyv4rH5IvwmHW8pjAStbc86cOTOnqh4SeEqAqWeJEw4EAwUMIBqF97eqY1JzgWsq-O3ylzXBHBQ7qu6ldAHAKCPN3eqIMcGkBH5cxQ07fU_QLoY5ZJvQuMzGozZakzLqjO9sRJ2dppUxucFGk13wKI8xLNsRdSHE3vlS9Fu0d3lEmw9vMbu6RMb3KGXTusl9W8GrS9yZbL3z96s7g5mSfXD9nlSfXr38ePYan7_bvDl7cY47ATTjQQw9s3SAhlLFGkZBUjCWKgEN1Lxm0nJJ667U27atezB0YFL1DShKpanZSfX8oLtb2tn2nfU5mknvoptN_KqDcfpPxLtRb8MXrYRkSjZF4Mm1QAyfF5uynl1aj2G8DUvSlCtZLABdZz3-i3oRlujLepqKRqpimTf_YRElBSOrFj2wuhhSina4sUxAr8HrQ_C6BK9_BK_3penR78vetPxMuhDYgZAK5Lc2_pr9D9nvjq66LQ</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Zhang, Cong-hui</creator><creator>Liu, Hong</creator><creator>Zhao, Wu-li</creator><creator>Zhao, Wen-xia</creator><creator>Zhou, Hui-min</creator><creator>Shao, Rong-guang</creator><general>Springer Singapore</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20211101</creationdate><title>G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin</title><author>Zhang, Cong-hui ; Liu, Hong ; Zhao, Wu-li ; Zhao, Wen-xia ; Zhou, Hui-min ; Shao, Rong-guang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-f5fd3e2f0922839320620ae28509074736e4627c206bbb7d0a2f368d908226a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>beta Catenin - antagonists & inhibitors</topic><topic>beta Catenin - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - physiology</topic><topic>Degradation</topic><topic>DNA Helicases - biosynthesis</topic><topic>Female</topic><topic>Glycogen Synthase Kinase 3 beta - antagonists & inhibitors</topic><topic>Glycogen Synthase Kinase 3 beta - metabolism</topic><topic>Humans</topic><topic>Immunology</topic><topic>Internal Medicine</topic><topic>MCF-7 Cells</topic><topic>Medical Microbiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Pharmacology/Toxicology</topic><topic>Phosphorylation</topic><topic>Poly-ADP-Ribose Binding Proteins - biosynthesis</topic><topic>Proteasomes</topic><topic>RNA Helicases - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Cong-hui</au><au>Liu, Hong</au><au>Zhao, Wu-li</au><au>Zhao, Wen-xia</au><au>Zhou, Hui-min</au><au>Shao, Rong-guang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacol Sin</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>42</volume><issue>11</issue><spage>1900</spage><epage>1912</epage><pages>1900-1912</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Ras-GTPase activating SH3 domain-binding protein 1 (G3BP1) is a multifunctional binding protein involved in the development of a variety of human cancers. However, the role of G3BP1 in breast cancer progression remains largely unknown. In this study, we report that G3BP1 is upregulated and correlated with poor prognosis in breast cancer. Overexpression of G3BP1 promotes breast cancer cell proliferation by stimulating β-catenin signaling, which upregulates a number of proliferation-related genes. We further show that G3BP1 improves the stability of β-catenin by inhibiting its ubiquitin-proteasome degradation rather than affecting the transcription of β-catenin. Mechanistically, elevated G3BP1 interacts with and inactivates GSK-3β to suppress β-catenin phosphorylation and degradation. Disturbing the G3BP1-GSK-3β interaction accelerates the degradation of β-catenin, impairing the proliferative capacity of breast cancer cells. Our study demonstrates that the regulatory mechanism of the G3BP1/GSK-3β/β-catenin axis may be a potential therapeutic target for breast cancer.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>33536604</pmid><doi>10.1038/s41401-020-00598-w</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals beta Catenin - antagonists & inhibitors beta Catenin - metabolism Biomedical and Life Sciences Biomedicine Breast cancer Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell growth Cell Line, Tumor Cell proliferation Cell Proliferation - physiology Degradation DNA Helicases - biosynthesis Female Glycogen Synthase Kinase 3 beta - antagonists & inhibitors Glycogen Synthase Kinase 3 beta - metabolism Humans Immunology Internal Medicine MCF-7 Cells Medical Microbiology Mice Mice, Inbred BALB C Mice, Nude Pharmacology/Toxicology Phosphorylation Poly-ADP-Ribose Binding Proteins - biosynthesis Proteasomes RNA Helicases - biosynthesis RNA Recognition Motif Proteins - biosynthesis Transcription Ubiquitin Vaccine Xenograft Model Antitumor Assays - methods β-Catenin |
| title | G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin |
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