WD repeat-containing protein 1 maintains β-Catenin activity to promote pancreatic cancer aggressiveness
Background The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages. Methods Eight-plex isobaric ta...
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| Veröffentlicht in: | British journal of cancer 2020-09, Vol.123 (6), p.1012-1023 |
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| creator | Li, Hengchao Liu, Xiaohui Jiang, Shuheng Zhou, Xinwen Yao, Lie Di, Yang Jiang, Yongjian Gu, Jichun Mao, Yishen Li, Ji Jin, Chen Yang, Pengyuan Fu, Deliang |
| description | Background
The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages.
Methods
Eight-plex isobaric tags coupled with two-dimensional liquid chromatography–tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation.
Results
A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/β-Catenin pathway; ectopic expression of a stabilised form of β-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of β-Catenin.
Conclusion
Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development. |
| doi_str_mv | 10.1038/s41416-020-0929-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7492282</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2442687736</sourcerecordid><originalsourceid>FETCH-LOGICAL-c498t-20ef4cb9c4166f6cbe8c900f153074bee6aa2050ceb2b0f891f8d7ac5c663f473</originalsourceid><addsrcrecordid>eNp9kU1uFDEQhS1ERCaBA7BBltiwaVJ2e_yzQUJDEpAisQGxtNxOdcfRtLuxPSPlWhyEM-HWhPAjwarsep-fXX6EPGfwmkGrz7JggskGODRguGngEVmxdcsbprl6TFYAoBYFjslJzrd1a0CrJ-S45RKYkHxFbr68owlndKXxUywuxBAHOqepYIiU0bF2lm6m3781G1ew6tT5Evah3NEyLehYYTq76FO1CZ76usRE3TAkzDnsMdbylBz1bpvx2X09JZ8vzj9t3jdXHy8_bN5eNV4YXRoO2AvfGV8Hk730HWpvAPo6FijRIUrnOKzBY8c76LVhvb5Wzq-9lG0vVHtK3hx851034rXHWJLb2jmF0aU7O7lg_1RiuLHDtLdKGM41rwav7g3S9HWHudgxZI_brYs47bLlghkwSom2oi__Qm-nXYp1vEqpdf19zvT_KcGlVqqVlWIHyqcp54T9w5MZ2CVte0jb1rTtkraFeubF77M-nPgZbwX4AchVigOmX1f_2_UHyp63Iw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2442687736</pqid></control><display><type>article</type><title>WD repeat-containing protein 1 maintains β-Catenin activity to promote pancreatic cancer aggressiveness</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Li, Hengchao ; Liu, Xiaohui ; Jiang, Shuheng ; Zhou, Xinwen ; Yao, Lie ; Di, Yang ; Jiang, Yongjian ; Gu, Jichun ; Mao, Yishen ; Li, Ji ; Jin, Chen ; Yang, Pengyuan ; Fu, Deliang</creator><creatorcontrib>Li, Hengchao ; Liu, Xiaohui ; Jiang, Shuheng ; Zhou, Xinwen ; Yao, Lie ; Di, Yang ; Jiang, Yongjian ; Gu, Jichun ; Mao, Yishen ; Li, Ji ; Jin, Chen ; Yang, Pengyuan ; Fu, Deliang</creatorcontrib><description>Background
The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages.
Methods
Eight-plex isobaric tags coupled with two-dimensional liquid chromatography–tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation.
Results
A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/β-Catenin pathway; ectopic expression of a stabilised form of β-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of β-Catenin.
Conclusion
Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-020-0929-0</identifier><identifier>PMID: 32601462</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/1647/2163 ; 692/4028/67/2332 ; Adenocarcinoma ; Animals ; beta Catenin - physiology ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Pancreatic Ductal - pathology ; Cell Line, Tumor ; Drug Resistance ; Ectopic expression ; Epidemiology ; Humans ; Immunoprecipitation ; Liquid chromatography ; Male ; Mass spectroscopy ; Metastases ; Metastasis ; Mice ; Microfilament Proteins - analysis ; Microfilament Proteins - antagonists & inhibitors ; Microfilament Proteins - physiology ; Molecular Medicine ; Oncology ; Pancreatic cancer ; Pancreatic Neoplasms - pathology ; Phenotypes ; Proteins ; Proteomes ; Tumorigenesis ; Tumors ; Ubiquitin-Specific Peptidase 7 - physiology ; Ubiquitination ; Western blotting ; Wnt protein ; Wnt Signaling Pathway - physiology ; β-Catenin</subject><ispartof>British journal of cancer, 2020-09, Vol.123 (6), p.1012-1023</ispartof><rights>The Author(s), under exclusive licence to Cancer Research UK 2020</rights><rights>The Author(s), under exclusive licence to Cancer Research UK 2020.</rights><rights>The Author(s), under exclusive licence to Cancer Research UK 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-20ef4cb9c4166f6cbe8c900f153074bee6aa2050ceb2b0f891f8d7ac5c663f473</citedby><cites>FETCH-LOGICAL-c498t-20ef4cb9c4166f6cbe8c900f153074bee6aa2050ceb2b0f891f8d7ac5c663f473</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/PMC7492282/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492282/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32601462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Hengchao</creatorcontrib><creatorcontrib>Liu, Xiaohui</creatorcontrib><creatorcontrib>Jiang, Shuheng</creatorcontrib><creatorcontrib>Zhou, Xinwen</creatorcontrib><creatorcontrib>Yao, Lie</creatorcontrib><creatorcontrib>Di, Yang</creatorcontrib><creatorcontrib>Jiang, Yongjian</creatorcontrib><creatorcontrib>Gu, Jichun</creatorcontrib><creatorcontrib>Mao, Yishen</creatorcontrib><creatorcontrib>Li, Ji</creatorcontrib><creatorcontrib>Jin, Chen</creatorcontrib><creatorcontrib>Yang, Pengyuan</creatorcontrib><creatorcontrib>Fu, Deliang</creatorcontrib><title>WD repeat-containing protein 1 maintains β-Catenin activity to promote pancreatic cancer aggressiveness</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages.
Methods
Eight-plex isobaric tags coupled with two-dimensional liquid chromatography–tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation.
Results
A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/β-Catenin pathway; ectopic expression of a stabilised form of β-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of β-Catenin.
Conclusion
Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development.</description><subject>631/1647/2163</subject><subject>692/4028/67/2332</subject><subject>Adenocarcinoma</subject><subject>Animals</subject><subject>beta Catenin - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Cell Line, Tumor</subject><subject>Drug Resistance</subject><subject>Ectopic expression</subject><subject>Epidemiology</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Liquid chromatography</subject><subject>Male</subject><subject>Mass spectroscopy</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Microfilament Proteins - analysis</subject><subject>Microfilament Proteins - antagonists & inhibitors</subject><subject>Microfilament Proteins - physiology</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Phenotypes</subject><subject>Proteins</subject><subject>Proteomes</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Ubiquitin-Specific Peptidase 7 - physiology</subject><subject>Ubiquitination</subject><subject>Western blotting</subject><subject>Wnt protein</subject><subject>Wnt Signaling Pathway - physiology</subject><subject>β-Catenin</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1uFDEQhS1ERCaBA7BBltiwaVJ2e_yzQUJDEpAisQGxtNxOdcfRtLuxPSPlWhyEM-HWhPAjwarsep-fXX6EPGfwmkGrz7JggskGODRguGngEVmxdcsbprl6TFYAoBYFjslJzrd1a0CrJ-S45RKYkHxFbr68owlndKXxUywuxBAHOqepYIiU0bF2lm6m3781G1ew6tT5Evah3NEyLehYYTq76FO1CZ76usRE3TAkzDnsMdbylBz1bpvx2X09JZ8vzj9t3jdXHy8_bN5eNV4YXRoO2AvfGV8Hk730HWpvAPo6FijRIUrnOKzBY8c76LVhvb5Wzq-9lG0vVHtK3hx851034rXHWJLb2jmF0aU7O7lg_1RiuLHDtLdKGM41rwav7g3S9HWHudgxZI_brYs47bLlghkwSom2oi__Qm-nXYp1vEqpdf19zvT_KcGlVqqVlWIHyqcp54T9w5MZ2CVte0jb1rTtkraFeubF77M-nPgZbwX4AchVigOmX1f_2_UHyp63Iw</recordid><startdate>20200915</startdate><enddate>20200915</enddate><creator>Li, Hengchao</creator><creator>Liu, Xiaohui</creator><creator>Jiang, Shuheng</creator><creator>Zhou, Xinwen</creator><creator>Yao, Lie</creator><creator>Di, Yang</creator><creator>Jiang, Yongjian</creator><creator>Gu, Jichun</creator><creator>Mao, Yishen</creator><creator>Li, Ji</creator><creator>Jin, Chen</creator><creator>Yang, Pengyuan</creator><creator>Fu, Deliang</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200915</creationdate><title>WD repeat-containing protein 1 maintains β-Catenin activity to promote pancreatic cancer aggressiveness</title><author>Li, Hengchao ; Liu, Xiaohui ; Jiang, Shuheng ; Zhou, Xinwen ; Yao, Lie ; Di, Yang ; Jiang, Yongjian ; Gu, Jichun ; Mao, Yishen ; Li, Ji ; Jin, Chen ; Yang, Pengyuan ; Fu, Deliang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-20ef4cb9c4166f6cbe8c900f153074bee6aa2050ceb2b0f891f8d7ac5c663f473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/1647/2163</topic><topic>692/4028/67/2332</topic><topic>Adenocarcinoma</topic><topic>Animals</topic><topic>beta Catenin - physiology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Cell Line, Tumor</topic><topic>Drug Resistance</topic><topic>Ectopic expression</topic><topic>Epidemiology</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Liquid chromatography</topic><topic>Male</topic><topic>Mass spectroscopy</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Microfilament Proteins - analysis</topic><topic>Microfilament Proteins - antagonists & inhibitors</topic><topic>Microfilament Proteins - physiology</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Phenotypes</topic><topic>Proteins</topic><topic>Proteomes</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Ubiquitin-Specific Peptidase 7 - physiology</topic><topic>Ubiquitination</topic><topic>Western blotting</topic><topic>Wnt protein</topic><topic>Wnt Signaling Pathway - physiology</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Hengchao</creatorcontrib><creatorcontrib>Liu, Xiaohui</creatorcontrib><creatorcontrib>Jiang, Shuheng</creatorcontrib><creatorcontrib>Zhou, Xinwen</creatorcontrib><creatorcontrib>Yao, Lie</creatorcontrib><creatorcontrib>Di, Yang</creatorcontrib><creatorcontrib>Jiang, Yongjian</creatorcontrib><creatorcontrib>Gu, Jichun</creatorcontrib><creatorcontrib>Mao, Yishen</creatorcontrib><creatorcontrib>Li, Ji</creatorcontrib><creatorcontrib>Jin, Chen</creatorcontrib><creatorcontrib>Yang, Pengyuan</creatorcontrib><creatorcontrib>Fu, Deliang</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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 China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Hengchao</au><au>Liu, Xiaohui</au><au>Jiang, Shuheng</au><au>Zhou, Xinwen</au><au>Yao, Lie</au><au>Di, Yang</au><au>Jiang, Yongjian</au><au>Gu, Jichun</au><au>Mao, Yishen</au><au>Li, Ji</au><au>Jin, Chen</au><au>Yang, Pengyuan</au><au>Fu, Deliang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>WD repeat-containing protein 1 maintains β-Catenin activity to promote pancreatic cancer aggressiveness</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2020-09-15</date><risdate>2020</risdate><volume>123</volume><issue>6</issue><spage>1012</spage><epage>1023</epage><pages>1012-1023</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><abstract>Background
The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages.
Methods
Eight-plex isobaric tags coupled with two-dimensional liquid chromatography–tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation.
Results
A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/β-Catenin pathway; ectopic expression of a stabilised form of β-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of β-Catenin.
Conclusion
Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32601462</pmid><doi>10.1038/s41416-020-0929-0</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2020-09, Vol.123 (6), p.1012-1023 |
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| source | MEDLINE; SpringerLink Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | 631/1647/2163 692/4028/67/2332 Adenocarcinoma Animals beta Catenin - physiology Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Pancreatic Ductal - pathology Cell Line, Tumor Drug Resistance Ectopic expression Epidemiology Humans Immunoprecipitation Liquid chromatography Male Mass spectroscopy Metastases Metastasis Mice Microfilament Proteins - analysis Microfilament Proteins - antagonists & inhibitors Microfilament Proteins - physiology Molecular Medicine Oncology Pancreatic cancer Pancreatic Neoplasms - pathology Phenotypes Proteins Proteomes Tumorigenesis Tumors Ubiquitin-Specific Peptidase 7 - physiology Ubiquitination Western blotting Wnt protein Wnt Signaling Pathway - physiology β-Catenin |
| title | WD repeat-containing protein 1 maintains β-Catenin activity to promote pancreatic cancer aggressiveness |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T03%3A12%3A38IST&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=WD%20repeat-containing%20protein%201%20maintains%20%CE%B2-Catenin%20activity%20to%20promote%20pancreatic%20cancer%20aggressiveness&rft.jtitle=British%20journal%20of%20cancer&rft.au=Li,%20Hengchao&rft.date=2020-09-15&rft.volume=123&rft.issue=6&rft.spage=1012&rft.epage=1023&rft.pages=1012-1023&rft.issn=0007-0920&rft.eissn=1532-1827&rft_id=info:doi/10.1038/s41416-020-0929-0&rft_dat=%3Cproquest_pubme%3E2442687736%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=2442687736&rft_id=info:pmid/32601462&rfr_iscdi=true |