Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis
Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3′‐phosphoadenosine 5′‐phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exac...
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Veröffentlicht in: | The FASEB journal 2020-08, Vol.34 (8), p.10316-10328 |
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description | Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3′‐phosphoadenosine 5′‐phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented FGFR1 signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 (SDC1) exhibited typical senescence phenotypes, and those depleted of PAPSS2‐, SDC1‐, or heparan sulfate 2‐O sulfotransferase 1 (HS2ST1) showed decreased FGFR1 internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)‐stimulated FGFR1‐ v‐akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin‐ and caveolin‐mediated FGFR1 endocytosis contributed to cellular senescence through the FGFR1‐AKT‐p53‐p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented FGFR1‐AKT‐p53‐p21 signaling, and decreased SDC1 expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of SDC1 expression and FGFR1 internalization, and an increase in FGFR1‐AKT‐p53‐p21 signaling. Together, our results demonstrate that properly sulfated SDC1 plays a critical role in preventing cellular senescence through the regulation of FGFR1 endocytosis. |
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We previously reported that silencing of 3′‐phosphoadenosine 5′‐phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented FGFR1 signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 (SDC1) exhibited typical senescence phenotypes, and those depleted of PAPSS2‐, SDC1‐, or heparan sulfate 2‐O sulfotransferase 1 (HS2ST1) showed decreased FGFR1 internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)‐stimulated FGFR1‐ v‐akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin‐ and caveolin‐mediated FGFR1 endocytosis contributed to cellular senescence through the FGFR1‐AKT‐p53‐p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented FGFR1‐AKT‐p53‐p21 signaling, and decreased SDC1 expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of SDC1 expression and FGFR1 internalization, and an increase in FGFR1‐AKT‐p53‐p21 signaling. Together, our results demonstrate that properly sulfated SDC1 plays a critical role in preventing cellular senescence through the regulation of FGFR1 endocytosis.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.201902714R</identifier><identifier>PMID: 32530114</identifier><language>eng</language><publisher>United States</publisher><subject>Caveolins - metabolism ; Cell Line ; Cell Line, Tumor ; cellular senescence ; Cellular Senescence - physiology ; Clathrin - metabolism ; endocytosis ; Endocytosis - physiology ; FGFR1 ; Fibroblast Growth Factor 2 - metabolism ; heparan sulfation ; Heparitin Sulfate - metabolism ; Humans ; MCF-7 Cells ; Receptor, Fibroblast Growth Factor, Type 1 - metabolism ; SDC1 ; Signal Transduction - physiology ; Sulfates - metabolism ; Syndecan-1 - metabolism</subject><ispartof>The FASEB journal, 2020-08, Vol.34 (8), p.10316-10328</ispartof><rights>2020 Federation of American Societies for Experimental Biology</rights><rights>2020 Federation of American Societies for Experimental Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3770-67a6216a7baffafa5b05e354a31f7284300e62c416e71d1d57452f1fa181bcd23</citedby><cites>FETCH-LOGICAL-c3770-67a6216a7baffafa5b05e354a31f7284300e62c416e71d1d57452f1fa181bcd23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.201902714R$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.201902714R$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32530114$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Donghee</creatorcontrib><creatorcontrib>Jung, Seung Hee</creatorcontrib><creatorcontrib>Lee, Gun‐Hee</creatorcontrib><creatorcontrib>Lee, Seongju</creatorcontrib><creatorcontrib>Park, Heon Joo</creatorcontrib><creatorcontrib>Ko, Young‐Gyu</creatorcontrib><creatorcontrib>Kim, Yong‐Nyun</creatorcontrib><creatorcontrib>Lee, Jae‐Seon</creatorcontrib><title>Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3′‐phosphoadenosine 5′‐phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented FGFR1 signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 (SDC1) exhibited typical senescence phenotypes, and those depleted of PAPSS2‐, SDC1‐, or heparan sulfate 2‐O sulfotransferase 1 (HS2ST1) showed decreased FGFR1 internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)‐stimulated FGFR1‐ v‐akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin‐ and caveolin‐mediated FGFR1 endocytosis contributed to cellular senescence through the FGFR1‐AKT‐p53‐p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented FGFR1‐AKT‐p53‐p21 signaling, and decreased SDC1 expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of SDC1 expression and FGFR1 internalization, and an increase in FGFR1‐AKT‐p53‐p21 signaling. Together, our results demonstrate that properly sulfated SDC1 plays a critical role in preventing cellular senescence through the regulation of FGFR1 endocytosis.</description><subject>Caveolins - metabolism</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>cellular senescence</subject><subject>Cellular Senescence - physiology</subject><subject>Clathrin - metabolism</subject><subject>endocytosis</subject><subject>Endocytosis - physiology</subject><subject>FGFR1</subject><subject>Fibroblast Growth Factor 2 - metabolism</subject><subject>heparan sulfation</subject><subject>Heparitin Sulfate - metabolism</subject><subject>Humans</subject><subject>MCF-7 Cells</subject><subject>Receptor, Fibroblast Growth Factor, Type 1 - metabolism</subject><subject>SDC1</subject><subject>Signal Transduction - physiology</subject><subject>Sulfates - metabolism</subject><subject>Syndecan-1 - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EFP3DAQBWCralW2wJFr5WMvgRk7sbNHQNAiIVUq7TlynDF4lY0X22GVA_-92S6FG6cZjT49aR5jJwinCEt15lanAnAJQmP56wNbYCWhULWCj2wB9VIUSsn6gH1JaQUACKg-swMpZoVYLtjz3dg7k6njaRo6smbgyH3iNvrsrel5DnwT6YmG7Id7bqnvx95EnmigZGmwxNuJr0M3X_8J59sY2t6kzO9j2OYH7ozNIfJIlja7hYYu2CmH5NMR--RMn-j4ZR6yP9dXvy9_FLc_v99cnt8WVmo9v6ONEqiMbo1zxpmqhYpkVRqJTou6lACkhC1RkcYOu0qXlXDoDNbY2k7IQ_Ztn7uJ4XGklJu1T7tfzEBhTI0oUSznDkU902JPbQwpRXLNJvq1iVOD0Owab9yqeWt89l9fosd2Td2r_l_xDMo92PqepvfTmuu7CyFAA8i_otiN5g</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Kang, Donghee</creator><creator>Jung, Seung Hee</creator><creator>Lee, Gun‐Hee</creator><creator>Lee, Seongju</creator><creator>Park, Heon Joo</creator><creator>Ko, Young‐Gyu</creator><creator>Kim, Yong‐Nyun</creator><creator>Lee, Jae‐Seon</creator><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></search><sort><creationdate>202008</creationdate><title>Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis</title><author>Kang, Donghee ; Jung, Seung Hee ; Lee, Gun‐Hee ; Lee, Seongju ; Park, Heon Joo ; Ko, Young‐Gyu ; Kim, Yong‐Nyun ; Lee, Jae‐Seon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3770-67a6216a7baffafa5b05e354a31f7284300e62c416e71d1d57452f1fa181bcd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Caveolins - metabolism</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>cellular senescence</topic><topic>Cellular Senescence - physiology</topic><topic>Clathrin - metabolism</topic><topic>endocytosis</topic><topic>Endocytosis - physiology</topic><topic>FGFR1</topic><topic>Fibroblast Growth Factor 2 - metabolism</topic><topic>heparan sulfation</topic><topic>Heparitin Sulfate - metabolism</topic><topic>Humans</topic><topic>MCF-7 Cells</topic><topic>Receptor, Fibroblast Growth Factor, Type 1 - metabolism</topic><topic>SDC1</topic><topic>Signal Transduction - physiology</topic><topic>Sulfates - metabolism</topic><topic>Syndecan-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Donghee</creatorcontrib><creatorcontrib>Jung, Seung Hee</creatorcontrib><creatorcontrib>Lee, Gun‐Hee</creatorcontrib><creatorcontrib>Lee, Seongju</creatorcontrib><creatorcontrib>Park, Heon Joo</creatorcontrib><creatorcontrib>Ko, Young‐Gyu</creatorcontrib><creatorcontrib>Kim, Yong‐Nyun</creatorcontrib><creatorcontrib>Lee, Jae‐Seon</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><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Donghee</au><au>Jung, Seung Hee</au><au>Lee, Gun‐Hee</au><au>Lee, Seongju</au><au>Park, Heon Joo</au><au>Ko, Young‐Gyu</au><au>Kim, Yong‐Nyun</au><au>Lee, Jae‐Seon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2020-08</date><risdate>2020</risdate><volume>34</volume><issue>8</issue><spage>10316</spage><epage>10328</epage><pages>10316-10328</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3′‐phosphoadenosine 5′‐phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented FGFR1 signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 (SDC1) exhibited typical senescence phenotypes, and those depleted of PAPSS2‐, SDC1‐, or heparan sulfate 2‐O sulfotransferase 1 (HS2ST1) showed decreased FGFR1 internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)‐stimulated FGFR1‐ v‐akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin‐ and caveolin‐mediated FGFR1 endocytosis contributed to cellular senescence through the FGFR1‐AKT‐p53‐p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented FGFR1‐AKT‐p53‐p21 signaling, and decreased SDC1 expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of SDC1 expression and FGFR1 internalization, and an increase in FGFR1‐AKT‐p53‐p21 signaling. Together, our results demonstrate that properly sulfated SDC1 plays a critical role in preventing cellular senescence through the regulation of FGFR1 endocytosis.</abstract><cop>United States</cop><pmid>32530114</pmid><doi>10.1096/fj.201902714R</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Caveolins - metabolism Cell Line Cell Line, Tumor cellular senescence Cellular Senescence - physiology Clathrin - metabolism endocytosis Endocytosis - physiology FGFR1 Fibroblast Growth Factor 2 - metabolism heparan sulfation Heparitin Sulfate - metabolism Humans MCF-7 Cells Receptor, Fibroblast Growth Factor, Type 1 - metabolism SDC1 Signal Transduction - physiology Sulfates - metabolism Syndecan-1 - metabolism |
title | Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis |
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