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UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer
The mTORC2 pathway plays a critical role in promoting tumor progression in human colorectal cancer (CRC). The regulatory mechanisms for this signaling pathway are only partially understood. We previously identified UBXN2A as a novel tumor suppressor protein in CRCs and hypothesized that UBXN2A suppr...
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| Published in: | Oncogene 2023-05, Vol.42 (21), p.1763-1776 |
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| container_end_page | 1776 |
| container_issue | 21 |
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| container_title | Oncogene |
| container_volume | 42 |
| creator | Sane, Sanam Srinivasan, Rekha Potts, Rashaun A Eikanger, Morgan Zagirova, Diana Freeling, Jessica Reihe, Casey A Antony, Ryan M Gupta, Brij K Lynch, Douglas Bleeker, Jonathan Turaihi, Hassan Pillatzki, Angela Zhou, Wei Luo, Xu Linnebacher, Michael Agany, Diing Zohim, Etienne Gnimpieba Humphrey, Lisa E Black, Adrian R Rezvani, Khosrow |
| description | The mTORC2 pathway plays a critical role in promoting tumor progression in human colorectal cancer (CRC). The regulatory mechanisms for this signaling pathway are only partially understood. We previously identified UBXN2A as a novel tumor suppressor protein in CRCs and hypothesized that UBXN2A suppresses the mTORC2 pathway, thereby inhibiting CRC growth and metastasis. We first used murine models to show that haploinsufficiency of UBXN2A significantly increases colon tumorigenesis. Induction of UBXN2A reduces AKT phosphorylation downstream of the mTORC2 pathway, which is essential for a plethora of cellular processes, including cell migration. Meanwhile, mTORC1 activities remain unchanged in the presence of UBXN2A. Mechanistic studies revealed that UBXN2A targets Rictor protein, a key component of the mTORC2 complex, for 26S proteasomal degradation. A set of genetic, pharmacological, and rescue experiments showed that UBXN2A regulates cell proliferation, apoptosis, migration, and colon cancer stem cells (CSCs) in CRC. CRC patients with a high level of UBXN2A have significantly better survival, and high-grade CRC tissues exhibit decreased UBXN2A protein expression. A high level of UBXN2A in patient-derived xenografts and tumor organoids decreases Rictor protein and suppresses the mTORC2 pathway. These findings provide new insights into the functions of an ubiquitin-like protein by inhibiting a dominant oncogenic pathway in CRC. |
| doi_str_mv | 10.1038/s41388-023-02686-7 |
| format | article |
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The regulatory mechanisms for this signaling pathway are only partially understood. We previously identified UBXN2A as a novel tumor suppressor protein in CRCs and hypothesized that UBXN2A suppresses the mTORC2 pathway, thereby inhibiting CRC growth and metastasis. We first used murine models to show that haploinsufficiency of UBXN2A significantly increases colon tumorigenesis. Induction of UBXN2A reduces AKT phosphorylation downstream of the mTORC2 pathway, which is essential for a plethora of cellular processes, including cell migration. Meanwhile, mTORC1 activities remain unchanged in the presence of UBXN2A. Mechanistic studies revealed that UBXN2A targets Rictor protein, a key component of the mTORC2 complex, for 26S proteasomal degradation. A set of genetic, pharmacological, and rescue experiments showed that UBXN2A regulates cell proliferation, apoptosis, migration, and colon cancer stem cells (CSCs) in CRC. CRC patients with a high level of UBXN2A have significantly better survival, and high-grade CRC tissues exhibit decreased UBXN2A protein expression. A high level of UBXN2A in patient-derived xenografts and tumor organoids decreases Rictor protein and suppresses the mTORC2 pathway. These findings provide new insights into the functions of an ubiquitin-like protein by inhibiting a dominant oncogenic pathway in CRC.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-023-02686-7</identifier><identifier>PMID: 37037900</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>AKT protein ; Animal models ; Animals ; Apoptosis ; Carcinogenesis - genetics ; Cell Line, Tumor ; Cell migration ; Cell proliferation ; Colon cancer ; Colonic Neoplasms - pathology ; Colorectal cancer ; Colorectal carcinoma ; Haploinsufficiency ; Humans ; Mechanistic Target of Rapamycin Complex 2 - metabolism ; Metastases ; Mice ; Neoplastic Stem Cells - pathology ; Organoids ; Phosphorylation ; Proteasomes ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Rapamycin-Insensitive Companion of mTOR Protein - genetics ; Rapamycin-Insensitive Companion of mTOR Protein - metabolism ; Signal Transduction ; Transcription Factors - genetics ; Tumor suppressor genes ; Tumorigenesis ; Ubiquitin ; Ubiquitins - metabolism</subject><ispartof>Oncogene, 2023-05, Vol.42 (21), p.1763-1776</ispartof><rights>2023. The Author(s), under exclusive licence to Springer Nature Limited.</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-85eca7a2a2d1750a4cb99a1ed261f4832b6de9e013ffe8eae75978dfff8a53253</citedby><cites>FETCH-LOGICAL-c431t-85eca7a2a2d1750a4cb99a1ed261f4832b6de9e013ffe8eae75978dfff8a53253</cites><orcidid>0000-0003-1560-6921 ; 0000-0001-8054-1402</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37037900$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sane, Sanam</creatorcontrib><creatorcontrib>Srinivasan, Rekha</creatorcontrib><creatorcontrib>Potts, Rashaun A</creatorcontrib><creatorcontrib>Eikanger, Morgan</creatorcontrib><creatorcontrib>Zagirova, Diana</creatorcontrib><creatorcontrib>Freeling, Jessica</creatorcontrib><creatorcontrib>Reihe, Casey A</creatorcontrib><creatorcontrib>Antony, Ryan M</creatorcontrib><creatorcontrib>Gupta, Brij K</creatorcontrib><creatorcontrib>Lynch, Douglas</creatorcontrib><creatorcontrib>Bleeker, Jonathan</creatorcontrib><creatorcontrib>Turaihi, Hassan</creatorcontrib><creatorcontrib>Pillatzki, Angela</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Luo, Xu</creatorcontrib><creatorcontrib>Linnebacher, Michael</creatorcontrib><creatorcontrib>Agany, Diing</creatorcontrib><creatorcontrib>Zohim, Etienne Gnimpieba</creatorcontrib><creatorcontrib>Humphrey, Lisa E</creatorcontrib><creatorcontrib>Black, Adrian R</creatorcontrib><creatorcontrib>Rezvani, Khosrow</creatorcontrib><title>UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>The mTORC2 pathway plays a critical role in promoting tumor progression in human colorectal cancer (CRC). The regulatory mechanisms for this signaling pathway are only partially understood. We previously identified UBXN2A as a novel tumor suppressor protein in CRCs and hypothesized that UBXN2A suppresses the mTORC2 pathway, thereby inhibiting CRC growth and metastasis. We first used murine models to show that haploinsufficiency of UBXN2A significantly increases colon tumorigenesis. Induction of UBXN2A reduces AKT phosphorylation downstream of the mTORC2 pathway, which is essential for a plethora of cellular processes, including cell migration. Meanwhile, mTORC1 activities remain unchanged in the presence of UBXN2A. Mechanistic studies revealed that UBXN2A targets Rictor protein, a key component of the mTORC2 complex, for 26S proteasomal degradation. A set of genetic, pharmacological, and rescue experiments showed that UBXN2A regulates cell proliferation, apoptosis, migration, and colon cancer stem cells (CSCs) in CRC. CRC patients with a high level of UBXN2A have significantly better survival, and high-grade CRC tissues exhibit decreased UBXN2A protein expression. A high level of UBXN2A in patient-derived xenografts and tumor organoids decreases Rictor protein and suppresses the mTORC2 pathway. These findings provide new insights into the functions of an ubiquitin-like protein by inhibiting a dominant oncogenic pathway in CRC.</description><subject>AKT protein</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Carcinogenesis - genetics</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Haploinsufficiency</subject><subject>Humans</subject><subject>Mechanistic Target of Rapamycin Complex 2 - metabolism</subject><subject>Metastases</subject><subject>Mice</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Organoids</subject><subject>Phosphorylation</subject><subject>Proteasomes</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Rapamycin-Insensitive Companion of mTOR Protein - genetics</subject><subject>Rapamycin-Insensitive Companion of mTOR Protein - metabolism</subject><subject>Signal Transduction</subject><subject>Transcription Factors - genetics</subject><subject>Tumor suppressor genes</subject><subject>Tumorigenesis</subject><subject>Ubiquitin</subject><subject>Ubiquitins - metabolism</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpdkU1r3DAQhkVpaLZp_0APRdBLD3WjD9uSTiVZ2rQQEggJ9CZm5fFawbZcyW7Jv4-2m4Q2ByHBPHqYmZeQd5x95kzq41RyqXXBhMyn1nWhXpAVL1VdVJUpX5IVMxUrjJDikLxO6ZYxpgwTr8ihVEzmJ1uR-eb054U4oWmZpogpYaJzh_TKuznEYri-vFoLmvx2hN6PWzrB3P2Bu08URopphk3vU4cNnZchRL_F0btHhvqRdsuQQRf6ENHN0FMHo8P4hhy00Cd8-3AfkZtvX6_X34vzy7Mf65PzwpWSz4Wu0IECAaLhqmJQuo0xwLERNW9LLcWmbtAg47JtUSOgqozSTdu2GiopKnlEvuy907IZsHE4zhF6O0U_QLyzAbz9vzL6zm7Db8uZ0IrVO8PHB0MMv5Y8sR18ctj3MGJYkhXKGC0qpVVGPzxDb8MS894ypbkS2Wd4psSecjGkFLF96oYzu0vV7lO1OVX7N1W7U7__d46nL48xyns445-7</recordid><startdate>20230522</startdate><enddate>20230522</enddate><creator>Sane, Sanam</creator><creator>Srinivasan, Rekha</creator><creator>Potts, Rashaun A</creator><creator>Eikanger, Morgan</creator><creator>Zagirova, Diana</creator><creator>Freeling, Jessica</creator><creator>Reihe, Casey A</creator><creator>Antony, Ryan M</creator><creator>Gupta, Brij K</creator><creator>Lynch, Douglas</creator><creator>Bleeker, Jonathan</creator><creator>Turaihi, Hassan</creator><creator>Pillatzki, Angela</creator><creator>Zhou, Wei</creator><creator>Luo, Xu</creator><creator>Linnebacher, Michael</creator><creator>Agany, Diing</creator><creator>Zohim, Etienne Gnimpieba</creator><creator>Humphrey, Lisa E</creator><creator>Black, Adrian R</creator><creator>Rezvani, Khosrow</creator><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>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1560-6921</orcidid><orcidid>https://orcid.org/0000-0001-8054-1402</orcidid></search><sort><creationdate>20230522</creationdate><title>UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer</title><author>Sane, Sanam ; Srinivasan, Rekha ; Potts, Rashaun A ; Eikanger, Morgan ; Zagirova, Diana ; Freeling, Jessica ; Reihe, Casey A ; Antony, Ryan M ; Gupta, Brij K ; Lynch, Douglas ; Bleeker, Jonathan ; Turaihi, Hassan ; Pillatzki, Angela ; Zhou, Wei ; Luo, Xu ; Linnebacher, Michael ; Agany, Diing ; Zohim, Etienne Gnimpieba ; Humphrey, Lisa E ; Black, Adrian R ; Rezvani, Khosrow</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-85eca7a2a2d1750a4cb99a1ed261f4832b6de9e013ffe8eae75978dfff8a53253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>AKT protein</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Carcinogenesis - genetics</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell proliferation</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Haploinsufficiency</topic><topic>Humans</topic><topic>Mechanistic Target of Rapamycin Complex 2 - metabolism</topic><topic>Metastases</topic><topic>Mice</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Organoids</topic><topic>Phosphorylation</topic><topic>Proteasomes</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rapamycin-Insensitive Companion of mTOR Protein - genetics</topic><topic>Rapamycin-Insensitive Companion of mTOR Protein - metabolism</topic><topic>Signal Transduction</topic><topic>Transcription Factors - genetics</topic><topic>Tumor suppressor genes</topic><topic>Tumorigenesis</topic><topic>Ubiquitin</topic><topic>Ubiquitins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sane, Sanam</creatorcontrib><creatorcontrib>Srinivasan, Rekha</creatorcontrib><creatorcontrib>Potts, Rashaun A</creatorcontrib><creatorcontrib>Eikanger, Morgan</creatorcontrib><creatorcontrib>Zagirova, Diana</creatorcontrib><creatorcontrib>Freeling, Jessica</creatorcontrib><creatorcontrib>Reihe, Casey A</creatorcontrib><creatorcontrib>Antony, Ryan M</creatorcontrib><creatorcontrib>Gupta, Brij K</creatorcontrib><creatorcontrib>Lynch, Douglas</creatorcontrib><creatorcontrib>Bleeker, Jonathan</creatorcontrib><creatorcontrib>Turaihi, Hassan</creatorcontrib><creatorcontrib>Pillatzki, Angela</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Luo, Xu</creatorcontrib><creatorcontrib>Linnebacher, Michael</creatorcontrib><creatorcontrib>Agany, Diing</creatorcontrib><creatorcontrib>Zohim, Etienne Gnimpieba</creatorcontrib><creatorcontrib>Humphrey, Lisa E</creatorcontrib><creatorcontrib>Black, Adrian R</creatorcontrib><creatorcontrib>Rezvani, Khosrow</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</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 Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest research library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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 Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sane, Sanam</au><au>Srinivasan, Rekha</au><au>Potts, Rashaun A</au><au>Eikanger, Morgan</au><au>Zagirova, Diana</au><au>Freeling, Jessica</au><au>Reihe, Casey A</au><au>Antony, Ryan M</au><au>Gupta, Brij K</au><au>Lynch, Douglas</au><au>Bleeker, Jonathan</au><au>Turaihi, Hassan</au><au>Pillatzki, Angela</au><au>Zhou, Wei</au><au>Luo, Xu</au><au>Linnebacher, Michael</au><au>Agany, Diing</au><au>Zohim, Etienne Gnimpieba</au><au>Humphrey, Lisa E</au><au>Black, Adrian R</au><au>Rezvani, Khosrow</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2023-05-22</date><risdate>2023</risdate><volume>42</volume><issue>21</issue><spage>1763</spage><epage>1776</epage><pages>1763-1776</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>AUTHOR CONTRIBUTIONS</notes><notes>All authors contributed to designing, performing, or analyzing the experiments. The work was supervised by KR and KR wrote the manuscript. All authors took part in editing the manuscript.</notes><abstract>The mTORC2 pathway plays a critical role in promoting tumor progression in human colorectal cancer (CRC). The regulatory mechanisms for this signaling pathway are only partially understood. We previously identified UBXN2A as a novel tumor suppressor protein in CRCs and hypothesized that UBXN2A suppresses the mTORC2 pathway, thereby inhibiting CRC growth and metastasis. We first used murine models to show that haploinsufficiency of UBXN2A significantly increases colon tumorigenesis. Induction of UBXN2A reduces AKT phosphorylation downstream of the mTORC2 pathway, which is essential for a plethora of cellular processes, including cell migration. Meanwhile, mTORC1 activities remain unchanged in the presence of UBXN2A. Mechanistic studies revealed that UBXN2A targets Rictor protein, a key component of the mTORC2 complex, for 26S proteasomal degradation. A set of genetic, pharmacological, and rescue experiments showed that UBXN2A regulates cell proliferation, apoptosis, migration, and colon cancer stem cells (CSCs) in CRC. CRC patients with a high level of UBXN2A have significantly better survival, and high-grade CRC tissues exhibit decreased UBXN2A protein expression. A high level of UBXN2A in patient-derived xenografts and tumor organoids decreases Rictor protein and suppresses the mTORC2 pathway. These findings provide new insights into the functions of an ubiquitin-like protein by inhibiting a dominant oncogenic pathway in CRC.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>37037900</pmid><doi>10.1038/s41388-023-02686-7</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-1560-6921</orcidid><orcidid>https://orcid.org/0000-0001-8054-1402</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2023-05, Vol.42 (21), p.1763-1776 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10287065 |
| source | Nexis UK; Springer Link |
| subjects | AKT protein Animal models Animals Apoptosis Carcinogenesis - genetics Cell Line, Tumor Cell migration Cell proliferation Colon cancer Colonic Neoplasms - pathology Colorectal cancer Colorectal carcinoma Haploinsufficiency Humans Mechanistic Target of Rapamycin Complex 2 - metabolism Metastases Mice Neoplastic Stem Cells - pathology Organoids Phosphorylation Proteasomes Proteins Proto-Oncogene Proteins c-akt - metabolism Rapamycin-Insensitive Companion of mTOR Protein - genetics Rapamycin-Insensitive Companion of mTOR Protein - metabolism Signal Transduction Transcription Factors - genetics Tumor suppressor genes Tumorigenesis Ubiquitin Ubiquitins - metabolism |
| title | UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T03%3A20%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=UBXN2A%20suppresses%20the%20Rictor-mTORC2%20signaling%20pathway,%20an%20established%20tumorigenic%20pathway%20in%20human%20colorectal%20cancer&rft.jtitle=Oncogene&rft.au=Sane,%20Sanam&rft.date=2023-05-22&rft.volume=42&rft.issue=21&rft.spage=1763&rft.epage=1776&rft.pages=1763-1776&rft.issn=0950-9232&rft.eissn=1476-5594&rft_id=info:doi/10.1038/s41388-023-02686-7&rft_dat=%3Cproquest_pubme%3E2799825787%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c431t-85eca7a2a2d1750a4cb99a1ed261f4832b6de9e013ffe8eae75978dfff8a53253%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2817270691&rft_id=info:pmid/37037900&rfr_iscdi=true |