Prolyl endopeptidase inhibitor Y-29794 blocks the IRS1-AKT-mTORC1 pathway and inhibits survival and in vivo tumor growth of triple-negative breast cancer
Prolyl endopeptidase (PREP), also known as prolyl oligopeptidase (POP), is an enzyme that cleaves short peptides (
Gespeichert in:
| Veröffentlicht in: | Cancer biology & therapy 2020-11, Vol.21 (11), p.1033-1040 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1040 |
|---|---|
| container_issue | 11 |
| container_start_page | 1033 |
| container_title | Cancer biology & therapy |
| container_volume | 21 |
| creator | Perez, Ricardo E Calhoun, Sarah Shim, Daeun Levenson, Victor V. Duan, Lei Maki, Carl G. |
| description | Prolyl endopeptidase (PREP), also known as prolyl oligopeptidase (POP), is an enzyme that cleaves short peptides ( |
| doi_str_mv | 10.1080/15384047.2020.1824989 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_33044914</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2450651519</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3839-f247d1512d4145cf08542233b2c44f18ca0ca5dff886d3fccc99c1072706ccc43</originalsourceid><addsrcrecordid>eNp9kcuO0zAUhiMEYi7wCCAv2WTwNbE3iFHFZcRIg4ayYGU5jt0anDjYTqs-yrwtrtqOYMPKPsf__58jf1X1CsErBDl8ixjhFNL2CkNcWhxTwcWT6hwxxmrO2ubp_k54vRedVRcp_YQQt7gRz6szQiClAtHz6uFrDH7ngRn7MJkpu14lA9y4dp3LIYIfNRatoKDzQf9KIK8NuLn_hurrL8t6WN7dLxCYVF5v1Q6osT8ZE0hz3LiN8scuKEUAeR5K5CqGbV6DYEGObvKmHs1KZbcxoItGpQy0GrWJL6pnVvlkXh7Py-r7xw_Lxef69u7TzeL6ttaEE1FbTNseMYR7iijTFnJGMSakw5pSi7hWUCvWW8t50xOrtRZCI9jiFjaloOSyenfIneZuML02Y47Kyym6QcWdDMrJf19Gt5arsJFt03JBcAl4cwyI4fdsUpaDS9p4r0YT5iQxZbBhZUVRpOwg1TGkFI19HIOg3GOVJ6xyj1UesRbf6793fHSdOBbB-4PAjTbEQW1D9L3MaudDtLH8p0uS_H_GHz0Xs9s</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2450651519</pqid></control><display><type>article</type><title>Prolyl endopeptidase inhibitor Y-29794 blocks the IRS1-AKT-mTORC1 pathway and inhibits survival and in vivo tumor growth of triple-negative breast cancer</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Perez, Ricardo E ; Calhoun, Sarah ; Shim, Daeun ; Levenson, Victor V. ; Duan, Lei ; Maki, Carl G.</creator><creatorcontrib>Perez, Ricardo E ; Calhoun, Sarah ; Shim, Daeun ; Levenson, Victor V. ; Duan, Lei ; Maki, Carl G.</creatorcontrib><description>Prolyl endopeptidase (PREP), also known as prolyl oligopeptidase (POP), is an enzyme that cleaves short peptides (<30 amino acids in length) on the C-terminal side of proline. PREP is highly expressed in multiple carcinomas and is a potential target for cancer therapy. A potent inhibitor of PREP, Y-29794, causes long-lasting inhibition of PREP in mouse tissues. However, there are no reports on Y-29794 effects on cancer cell and tumor proliferation. Using cell line models of aggressive triple-negative breast cancer (TNBC), we show here that Y-29794 inhibited proliferation and induced death in multiple TNBC cell lines. Cell death induced by Y-29794 coincided with inhibition of the IRS1-AKT-mTORC1 survival signaling pathway, although stable depletion of PREP alone was not sufficient to reduce IRS1-AKT-mTORC1 signaling or induce death. These results suggest that Y-29794 elicits its cancer cell killing effect by targeting other mechanisms in addition to PREP. Importantly, Y-29794 inhibited tumor growth when tested in xenograft models of TNBC in mice. Induction of cell death in culture and inhibition of xenograft tumor growth support the potential utility of Y-29794 or its derivatives as a treatment option for TNBC tumors.</description><identifier>ISSN: 1538-4047</identifier><identifier>ISSN: 1555-8576</identifier><identifier>EISSN: 1555-8576</identifier><identifier>DOI: 10.1080/15384047.2020.1824989</identifier><identifier>PMID: 33044914</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Disease Models, Animal ; Humans ; Insulin Receptor Substrate Proteins - metabolism ; IRS1-AKT-mTORC1 pathway ; Mice ; Mice, Nude ; Prolyl endopeptidase ; Prolyl Oligopeptidases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Research Paper ; Transfection ; Triple Negative Breast Neoplasms - genetics ; triple-negative breast cancer</subject><ispartof>Cancer biology & therapy, 2020-11, Vol.21 (11), p.1033-1040</ispartof><rights>2020 Taylor & Francis Group, LLC 2020</rights><rights>2020 Taylor & Francis Group, LLC 2020 Taylor & Francis</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3839-f247d1512d4145cf08542233b2c44f18ca0ca5dff886d3fccc99c1072706ccc43</citedby><cites>FETCH-LOGICAL-c3839-f247d1512d4145cf08542233b2c44f18ca0ca5dff886d3fccc99c1072706ccc43</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/PMC7678932/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678932/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33044914$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perez, Ricardo E</creatorcontrib><creatorcontrib>Calhoun, Sarah</creatorcontrib><creatorcontrib>Shim, Daeun</creatorcontrib><creatorcontrib>Levenson, Victor V.</creatorcontrib><creatorcontrib>Duan, Lei</creatorcontrib><creatorcontrib>Maki, Carl G.</creatorcontrib><title>Prolyl endopeptidase inhibitor Y-29794 blocks the IRS1-AKT-mTORC1 pathway and inhibits survival and in vivo tumor growth of triple-negative breast cancer</title><title>Cancer biology & therapy</title><addtitle>Cancer Biol Ther</addtitle><description>Prolyl endopeptidase (PREP), also known as prolyl oligopeptidase (POP), is an enzyme that cleaves short peptides (<30 amino acids in length) on the C-terminal side of proline. PREP is highly expressed in multiple carcinomas and is a potential target for cancer therapy. A potent inhibitor of PREP, Y-29794, causes long-lasting inhibition of PREP in mouse tissues. However, there are no reports on Y-29794 effects on cancer cell and tumor proliferation. Using cell line models of aggressive triple-negative breast cancer (TNBC), we show here that Y-29794 inhibited proliferation and induced death in multiple TNBC cell lines. Cell death induced by Y-29794 coincided with inhibition of the IRS1-AKT-mTORC1 survival signaling pathway, although stable depletion of PREP alone was not sufficient to reduce IRS1-AKT-mTORC1 signaling or induce death. These results suggest that Y-29794 elicits its cancer cell killing effect by targeting other mechanisms in addition to PREP. Importantly, Y-29794 inhibited tumor growth when tested in xenograft models of TNBC in mice. Induction of cell death in culture and inhibition of xenograft tumor growth support the potential utility of Y-29794 or its derivatives as a treatment option for TNBC tumors.</description><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>Humans</subject><subject>Insulin Receptor Substrate Proteins - metabolism</subject><subject>IRS1-AKT-mTORC1 pathway</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Prolyl endopeptidase</subject><subject>Prolyl Oligopeptidases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Research Paper</subject><subject>Transfection</subject><subject>Triple Negative Breast Neoplasms - genetics</subject><subject>triple-negative breast cancer</subject><issn>1538-4047</issn><issn>1555-8576</issn><issn>1555-8576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuO0zAUhiMEYi7wCCAv2WTwNbE3iFHFZcRIg4ayYGU5jt0anDjYTqs-yrwtrtqOYMPKPsf__58jf1X1CsErBDl8ixjhFNL2CkNcWhxTwcWT6hwxxmrO2ubp_k54vRedVRcp_YQQt7gRz6szQiClAtHz6uFrDH7ngRn7MJkpu14lA9y4dp3LIYIfNRatoKDzQf9KIK8NuLn_hurrL8t6WN7dLxCYVF5v1Q6osT8ZE0hz3LiN8scuKEUAeR5K5CqGbV6DYEGObvKmHs1KZbcxoItGpQy0GrWJL6pnVvlkXh7Py-r7xw_Lxef69u7TzeL6ttaEE1FbTNseMYR7iijTFnJGMSakw5pSi7hWUCvWW8t50xOrtRZCI9jiFjaloOSyenfIneZuML02Y47Kyym6QcWdDMrJf19Gt5arsJFt03JBcAl4cwyI4fdsUpaDS9p4r0YT5iQxZbBhZUVRpOwg1TGkFI19HIOg3GOVJ6xyj1UesRbf6793fHSdOBbB-4PAjTbEQW1D9L3MaudDtLH8p0uS_H_GHz0Xs9s</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Perez, Ricardo E</creator><creator>Calhoun, Sarah</creator><creator>Shim, Daeun</creator><creator>Levenson, Victor V.</creator><creator>Duan, Lei</creator><creator>Maki, Carl G.</creator><general>Taylor & Francis</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20201101</creationdate><title>Prolyl endopeptidase inhibitor Y-29794 blocks the IRS1-AKT-mTORC1 pathway and inhibits survival and in vivo tumor growth of triple-negative breast cancer</title><author>Perez, Ricardo E ; Calhoun, Sarah ; Shim, Daeun ; Levenson, Victor V. ; Duan, Lei ; Maki, Carl G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3839-f247d1512d4145cf08542233b2c44f18ca0ca5dff886d3fccc99c1072706ccc43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Disease Models, Animal</topic><topic>Humans</topic><topic>Insulin Receptor Substrate Proteins - metabolism</topic><topic>IRS1-AKT-mTORC1 pathway</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Prolyl endopeptidase</topic><topic>Prolyl Oligopeptidases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Research Paper</topic><topic>Transfection</topic><topic>Triple Negative Breast Neoplasms - genetics</topic><topic>triple-negative breast cancer</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perez, Ricardo E</creatorcontrib><creatorcontrib>Calhoun, Sarah</creatorcontrib><creatorcontrib>Shim, Daeun</creatorcontrib><creatorcontrib>Levenson, Victor V.</creatorcontrib><creatorcontrib>Duan, Lei</creatorcontrib><creatorcontrib>Maki, Carl G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer biology & therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perez, Ricardo E</au><au>Calhoun, Sarah</au><au>Shim, Daeun</au><au>Levenson, Victor V.</au><au>Duan, Lei</au><au>Maki, Carl G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prolyl endopeptidase inhibitor Y-29794 blocks the IRS1-AKT-mTORC1 pathway and inhibits survival and in vivo tumor growth of triple-negative breast cancer</atitle><jtitle>Cancer biology & therapy</jtitle><addtitle>Cancer Biol Ther</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>21</volume><issue>11</issue><spage>1033</spage><epage>1040</epage><pages>1033-1040</pages><issn>1538-4047</issn><issn>1555-8576</issn><eissn>1555-8576</eissn><abstract>Prolyl endopeptidase (PREP), also known as prolyl oligopeptidase (POP), is an enzyme that cleaves short peptides (<30 amino acids in length) on the C-terminal side of proline. PREP is highly expressed in multiple carcinomas and is a potential target for cancer therapy. A potent inhibitor of PREP, Y-29794, causes long-lasting inhibition of PREP in mouse tissues. However, there are no reports on Y-29794 effects on cancer cell and tumor proliferation. Using cell line models of aggressive triple-negative breast cancer (TNBC), we show here that Y-29794 inhibited proliferation and induced death in multiple TNBC cell lines. Cell death induced by Y-29794 coincided with inhibition of the IRS1-AKT-mTORC1 survival signaling pathway, although stable depletion of PREP alone was not sufficient to reduce IRS1-AKT-mTORC1 signaling or induce death. These results suggest that Y-29794 elicits its cancer cell killing effect by targeting other mechanisms in addition to PREP. Importantly, Y-29794 inhibited tumor growth when tested in xenograft models of TNBC in mice. Induction of cell death in culture and inhibition of xenograft tumor growth support the potential utility of Y-29794 or its derivatives as a treatment option for TNBC tumors.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>33044914</pmid><doi>10.1080/15384047.2020.1824989</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1538-4047 |
| ispartof | Cancer biology & therapy, 2020-11, Vol.21 (11), p.1033-1040 |
| issn | 1538-4047 1555-8576 1555-8576 |
| language | eng |
| recordid | cdi_pubmed_primary_33044914 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Disease Models, Animal Humans Insulin Receptor Substrate Proteins - metabolism IRS1-AKT-mTORC1 pathway Mice Mice, Nude Prolyl endopeptidase Prolyl Oligopeptidases - metabolism Proto-Oncogene Proteins c-akt - metabolism Research Paper Transfection Triple Negative Breast Neoplasms - genetics triple-negative breast cancer |
| title | Prolyl endopeptidase inhibitor Y-29794 blocks the IRS1-AKT-mTORC1 pathway and inhibits survival and in vivo tumor growth of triple-negative breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T09%3A06%3A54IST&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=Prolyl%20endopeptidase%20inhibitor%20Y-29794%20blocks%20the%20IRS1-AKT-mTORC1%20pathway%20and%20inhibits%20survival%20and%20in%20vivo%20tumor%20growth%20of%20triple-negative%20breast%20cancer&rft.jtitle=Cancer%20biology%20&%20therapy&rft.au=Perez,%20Ricardo%20E&rft.date=2020-11-01&rft.volume=21&rft.issue=11&rft.spage=1033&rft.epage=1040&rft.pages=1033-1040&rft.issn=1538-4047&rft.eissn=1555-8576&rft_id=info:doi/10.1080/15384047.2020.1824989&rft_dat=%3Cproquest_pubme%3E2450651519%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2450651519&rft_id=info:pmid/33044914&rfr_iscdi=true |