Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer
The ErbB3 receptor-binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubi...
Gespeichert in:
| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2017-04, Vol.77 (8), p.1983-1996 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1996 |
|---|---|
| container_issue | 8 |
| container_start_page | 1983 |
| container_title | Cancer research (Chicago, Ill.) |
| container_volume | 77 |
| creator | Wang, Yuli Zhang, Pengju Wang, Yunshan Zhan, Panpan Liu, Chunyan Mao, Jian-Hua Wei, Guangwei |
| description | The ErbB3 receptor-binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 P48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 P48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function. In contrast, EBP1 P42 bound to both the F-box domain of FBXW7 as well as FBXW7 substrates. This adapter function of EBP1 P42 stabilized the interaction of FBXW7 with its substrates and promoted FBXW7-mediated degradation of oncogenic targets, enhancing its overall tumor-suppressing function. Overall, our results establish distinct physical and functional interactions between FBXW7 and EBP1 isoforms, which yield their mechanistically unique isoform-specific functions of EBP1 in cancer.
. |
| doi_str_mv | 10.1158/0008-5472.CAN-16-2246 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5392370</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1983401763</sourcerecordid><originalsourceid>FETCH-LOGICAL-c466t-5d9140034d48a0eefd01c5c6e3158277e918a1535864bb57934a427024daf8e63</originalsourceid><addsrcrecordid>eNpVkUtPWzEUhC1UVAL0J7Sy2vUFv-27qURebSREuwDBznJ8fRtHiZ3aDoh_X0cJUVlZlmeOZ84HwGeMrjDm6hohpBrOJLka3dw1WDSEMHECBphT1UjG-AcwOGrOwHnOy3rlGPGP4IwoglqB2QA8jn0uPtgCZ6G4ZGzxMWQYezgZ_sZwlmMf0zrDF18WcDp8epRwsvLWlwzHvu9dcqHA6TYcfD7AkQnWpUtw2ptVdp8O5wV4mE7uRz-b218_ZqOb28YyIUrDuxYzhCjrmDLIub5D2HIrHK0diZSuxcrUSlwJNp9z2VJmGJGIsM70ygl6Ab7v526287XrbI2TzEpvkl-b9Kqj8fr9S_AL_Sc-a05bQiWqA77uB8S6B51rM2cXNobgbNE1m2JEVdG3wy8p_t26XPQyblOoxTRuFWUIS0Griu9VNsWck-uPMTDSO2h6B0TvgOgKTWOhd9Cq78v_HY6uN0r0H6d-kSs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983401763</pqid></control><display><type>article</type><title>Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Wang, Yuli ; Zhang, Pengju ; Wang, Yunshan ; Zhan, Panpan ; Liu, Chunyan ; Mao, Jian-Hua ; Wei, Guangwei</creator><creatorcontrib>Wang, Yuli ; Zhang, Pengju ; Wang, Yunshan ; Zhan, Panpan ; Liu, Chunyan ; Mao, Jian-Hua ; Wei, Guangwei ; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)</creatorcontrib><description>The ErbB3 receptor-binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 P48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 P48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function. In contrast, EBP1 P42 bound to both the F-box domain of FBXW7 as well as FBXW7 substrates. This adapter function of EBP1 P42 stabilized the interaction of FBXW7 with its substrates and promoted FBXW7-mediated degradation of oncogenic targets, enhancing its overall tumor-suppressing function. Overall, our results establish distinct physical and functional interactions between FBXW7 and EBP1 isoforms, which yield their mechanistically unique isoform-specific functions of EBP1 in cancer.
.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-16-2246</identifier><identifier>PMID: 28209614</identifier><language>eng</language><publisher>United States: American Association for Cancer Research, Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Alternative splicing ; Animals ; BASIC BIOLOGICAL SCIENCES ; Binding Sites ; Cancer ; Cdc4 protein ; Cell Cycle Proteins - deficiency ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; colorectal cancer ; Cytoplasm - metabolism ; Cytosol ; EBP1 P42 ; EBP1 P48 ; EBP1 protein ; ErbB-3 protein ; F-Box Proteins - genetics ; F-Box Proteins - metabolism ; F-Box-WD Repeat-Containing Protein 7 ; FBXW7 ; Glycogen Synthase Kinase 3 beta - metabolism ; HCT116 Cells ; HEK293 Cells ; Heterografts ; Humans ; Immunohistochemistry ; Isoforms ; Mice ; Mice, Nude ; Neoplasms - genetics ; Neoplasms - metabolism ; Neoplasms - pathology ; Phenotype ; Proteasome Endopeptidase Complex - metabolism ; Protein Interaction Maps ; protein isoform ; Protein Isoforms ; Proteins ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Substrates ; Tumor suppressor genes ; Tumorigenesis ; Ubiquitin ; Ubiquitin-protein ligase ; Ubiquitin-Protein Ligases - deficiency ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism</subject><ispartof>Cancer research (Chicago, Ill.), 2017-04, Vol.77 (8), p.1983-1996</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research, Inc. Apr 15, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-5d9140034d48a0eefd01c5c6e3158277e918a1535864bb57934a427024daf8e63</citedby><cites>FETCH-LOGICAL-c466t-5d9140034d48a0eefd01c5c6e3158277e918a1535864bb57934a427024daf8e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3342,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28209614$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/servlets/purl/1408428$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yuli</creatorcontrib><creatorcontrib>Zhang, Pengju</creatorcontrib><creatorcontrib>Wang, Yunshan</creatorcontrib><creatorcontrib>Zhan, Panpan</creatorcontrib><creatorcontrib>Liu, Chunyan</creatorcontrib><creatorcontrib>Mao, Jian-Hua</creatorcontrib><creatorcontrib>Wei, Guangwei</creatorcontrib><creatorcontrib>Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)</creatorcontrib><title>Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The ErbB3 receptor-binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 P48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 P48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function. In contrast, EBP1 P42 bound to both the F-box domain of FBXW7 as well as FBXW7 substrates. This adapter function of EBP1 P42 stabilized the interaction of FBXW7 with its substrates and promoted FBXW7-mediated degradation of oncogenic targets, enhancing its overall tumor-suppressing function. Overall, our results establish distinct physical and functional interactions between FBXW7 and EBP1 isoforms, which yield their mechanistically unique isoform-specific functions of EBP1 in cancer.
.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Alternative splicing</subject><subject>Animals</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Binding Sites</subject><subject>Cancer</subject><subject>Cdc4 protein</subject><subject>Cell Cycle Proteins - deficiency</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>colorectal cancer</subject><subject>Cytoplasm - metabolism</subject><subject>Cytosol</subject><subject>EBP1 P42</subject><subject>EBP1 P48</subject><subject>EBP1 protein</subject><subject>ErbB-3 protein</subject><subject>F-Box Proteins - genetics</subject><subject>F-Box Proteins - metabolism</subject><subject>F-Box-WD Repeat-Containing Protein 7</subject><subject>FBXW7</subject><subject>Glycogen Synthase Kinase 3 beta - metabolism</subject><subject>HCT116 Cells</subject><subject>HEK293 Cells</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Isoforms</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Phenotype</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Protein Interaction Maps</subject><subject>protein isoform</subject><subject>Protein Isoforms</subject><subject>Proteins</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Substrates</subject><subject>Tumor suppressor genes</subject><subject>Tumorigenesis</subject><subject>Ubiquitin</subject><subject>Ubiquitin-protein ligase</subject><subject>Ubiquitin-Protein Ligases - deficiency</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUtPWzEUhC1UVAL0J7Sy2vUFv-27qURebSREuwDBznJ8fRtHiZ3aDoh_X0cJUVlZlmeOZ84HwGeMrjDm6hohpBrOJLka3dw1WDSEMHECBphT1UjG-AcwOGrOwHnOy3rlGPGP4IwoglqB2QA8jn0uPtgCZ6G4ZGzxMWQYezgZ_sZwlmMf0zrDF18WcDp8epRwsvLWlwzHvu9dcqHA6TYcfD7AkQnWpUtw2ptVdp8O5wV4mE7uRz-b218_ZqOb28YyIUrDuxYzhCjrmDLIub5D2HIrHK0diZSuxcrUSlwJNp9z2VJmGJGIsM70ygl6Ab7v526287XrbI2TzEpvkl-b9Kqj8fr9S_AL_Sc-a05bQiWqA77uB8S6B51rM2cXNobgbNE1m2JEVdG3wy8p_t26XPQyblOoxTRuFWUIS0Griu9VNsWck-uPMTDSO2h6B0TvgOgKTWOhd9Cq78v_HY6uN0r0H6d-kSs</recordid><startdate>20170415</startdate><enddate>20170415</enddate><creator>Wang, Yuli</creator><creator>Zhang, Pengju</creator><creator>Wang, Yunshan</creator><creator>Zhan, Panpan</creator><creator>Liu, Chunyan</creator><creator>Mao, Jian-Hua</creator><creator>Wei, Guangwei</creator><general>American Association for Cancer Research, Inc</general><general>American Association for Cancer Research</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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>OIOZB</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20170415</creationdate><title>Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer</title><author>Wang, Yuli ; Zhang, Pengju ; Wang, Yunshan ; Zhan, Panpan ; Liu, Chunyan ; Mao, Jian-Hua ; Wei, Guangwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-5d9140034d48a0eefd01c5c6e3158277e918a1535864bb57934a427024daf8e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Alternative splicing</topic><topic>Animals</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Binding Sites</topic><topic>Cancer</topic><topic>Cdc4 protein</topic><topic>Cell Cycle Proteins - deficiency</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>colorectal cancer</topic><topic>Cytoplasm - metabolism</topic><topic>Cytosol</topic><topic>EBP1 P42</topic><topic>EBP1 P48</topic><topic>EBP1 protein</topic><topic>ErbB-3 protein</topic><topic>F-Box Proteins - genetics</topic><topic>F-Box Proteins - metabolism</topic><topic>F-Box-WD Repeat-Containing Protein 7</topic><topic>FBXW7</topic><topic>Glycogen Synthase Kinase 3 beta - metabolism</topic><topic>HCT116 Cells</topic><topic>HEK293 Cells</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Isoforms</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Phenotype</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Protein Interaction Maps</topic><topic>protein isoform</topic><topic>Protein Isoforms</topic><topic>Proteins</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Substrates</topic><topic>Tumor suppressor genes</topic><topic>Tumorigenesis</topic><topic>Ubiquitin</topic><topic>Ubiquitin-protein ligase</topic><topic>Ubiquitin-Protein Ligases - deficiency</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yuli</creatorcontrib><creatorcontrib>Zhang, Pengju</creatorcontrib><creatorcontrib>Wang, Yunshan</creatorcontrib><creatorcontrib>Zhan, Panpan</creatorcontrib><creatorcontrib>Liu, Chunyan</creatorcontrib><creatorcontrib>Mao, Jian-Hua</creatorcontrib><creatorcontrib>Wei, Guangwei</creatorcontrib><creatorcontrib>Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>OSTI.GOV - Hybrid</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yuli</au><au>Zhang, Pengju</au><au>Wang, Yunshan</au><au>Zhan, Panpan</au><au>Liu, Chunyan</au><au>Mao, Jian-Hua</au><au>Wei, Guangwei</au><aucorp>Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2017-04-15</date><risdate>2017</risdate><volume>77</volume><issue>8</issue><spage>1983</spage><epage>1996</epage><pages>1983-1996</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><abstract>The ErbB3 receptor-binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 P48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 P48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function. In contrast, EBP1 P42 bound to both the F-box domain of FBXW7 as well as FBXW7 substrates. This adapter function of EBP1 P42 stabilized the interaction of FBXW7 with its substrates and promoted FBXW7-mediated degradation of oncogenic targets, enhancing its overall tumor-suppressing function. Overall, our results establish distinct physical and functional interactions between FBXW7 and EBP1 isoforms, which yield their mechanistically unique isoform-specific functions of EBP1 in cancer.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research, Inc</pub><pmid>28209614</pmid><doi>10.1158/0008-5472.CAN-16-2246</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-5472 |
| ispartof | Cancer research (Chicago, Ill.), 2017-04, Vol.77 (8), p.1983-1996 |
| issn | 0008-5472 1538-7445 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5392370 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | 60 APPLIED LIFE SCIENCES Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Alternative splicing Animals BASIC BIOLOGICAL SCIENCES Binding Sites Cancer Cdc4 protein Cell Cycle Proteins - deficiency Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Line, Tumor colorectal cancer Cytoplasm - metabolism Cytosol EBP1 P42 EBP1 P48 EBP1 protein ErbB-3 protein F-Box Proteins - genetics F-Box Proteins - metabolism F-Box-WD Repeat-Containing Protein 7 FBXW7 Glycogen Synthase Kinase 3 beta - metabolism HCT116 Cells HEK293 Cells Heterografts Humans Immunohistochemistry Isoforms Mice Mice, Nude Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Phenotype Proteasome Endopeptidase Complex - metabolism Protein Interaction Maps protein isoform Protein Isoforms Proteins RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Substrates Tumor suppressor genes Tumorigenesis Ubiquitin Ubiquitin-protein ligase Ubiquitin-Protein Ligases - deficiency Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism |
| title | Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T20%3A10%3A42IST&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=Distinct%20Interactions%20of%20EBP1%20Isoforms%20with%20FBXW7%20Elicits%20Different%20Functions%20in%20Cancer&rft.jtitle=Cancer%20research%20(Chicago,%20Ill.)&rft.au=Wang,%20Yuli&rft.aucorp=Lawrence%20Berkeley%20National%20Lab.%20(LBNL),%20Berkeley,%20CA%20(United%20States)&rft.date=2017-04-15&rft.volume=77&rft.issue=8&rft.spage=1983&rft.epage=1996&rft.pages=1983-1996&rft.issn=0008-5472&rft.eissn=1538-7445&rft_id=info:doi/10.1158/0008-5472.CAN-16-2246&rft_dat=%3Cproquest_pubme%3E1983401763%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=1983401763&rft_id=info:pmid/28209614&rfr_iscdi=true |