Ubiquitin carboxyl-terminal hydrolase isozyme L1/UCHL1 suppresses epithelial–mesenchymal transition and is under-expressed in cadmium-transformed human bronchial epithelial cells
Cadmium (Cd), a highly toxic heavy metal, is widespreadly distributed in the environment. Chronic exposure to Cd is associated with the development of several diseases including cancers. Over the decade, many researches have been carried on various models to examine the acute effects of Cd; yet, lim...
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| Veröffentlicht in: | Cell biology and toxicology 2021-08, Vol.37 (4), p.497-513 |
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| creator | Wu, Dan-Dan Xu, Yan-Ming Chen, De-Ju Liang, Zhan-Ling Chen, Xu-Li Hylkema, Machteld N. Rots, Marianne G. Li, Sheng-Qing Lau, Andy T. Y. |
| description | Cadmium (Cd), a highly toxic heavy metal, is widespreadly distributed in the environment. Chronic exposure to Cd is associated with the development of several diseases including cancers. Over the decade, many researches have been carried on various models to examine the acute effects of Cd; yet, limited knowledge is known about the long-term Cd exposure, especially in the human lung cells. Previously, we showed that chronic Cd-exposed human bronchial epithelial BEAS-2B cells exhibited transformed cell properties, such as anchorage-independent growth, augmented cell migration, and epithelial–mesenchymal transition (EMT). To study these Cd-transformed cells more comprehensively, here, we further characterized their subproteomes. Overall, a total of 63 differentially expressed proteins between Cd-transformed and passage-matched control cells among the five subcellular fractions (cytoplasmic, membrane, nuclear-soluble, chromatin-bound, and cytoskeletal) were identified by mass spectrometric analysis and database searching. Interestingly, we found that the thiol protease ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) is one of the severely downregulated proteins in the Cd-transformed cells. Notably, the EMT phenotype of Cd-transformed cells can be suppressed by forced ectopic expression of UCHL1, suggesting UCHL1 as a crucial modulator in the maintenance of the proper differentiation status in lung epithelial cells. Since EMT is considered as a critical step during malignant cell transformation, finding novel cellular targets that can antagonize this transition may lead to more efficient strategies to inhibit cancer development. Our data report for the first time that UCHL1 may play a function in the suppression of EMT in Cd-transformed human lung epithelial cells, indicating that UCHL1 might be a new therapeutic target for chronic Cd-induced carcinogenesis.
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| doi_str_mv | 10.1007/s10565-020-09560-2 |
| format | Article |
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Graphical abstract</description><identifier>ISSN: 0742-2091</identifier><identifier>EISSN: 1573-6822</identifier><identifier>DOI: 10.1007/s10565-020-09560-2</identifier><identifier>PMID: 33040242</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Acute effects ; Biochemistry ; Biology ; Biomedical and Life Sciences ; Cadmium ; Cadmium - toxicity ; Cancer ; Carcinogenesis ; Carcinogens ; Cell adhesion & migration ; Cell Biology ; Cell differentiation ; Cell migration ; Cell Movement ; Chromatin ; Chronic exposure ; Cytoplasmic membranes ; Cytoskeleton ; Database searching ; DNA methylation ; Ectopic expression ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Epithelium ; Exposure ; Gene expression ; Heavy metals ; Humans ; Hydrolase ; Life Sciences ; Lungs ; Mesenchyme ; Original Article ; Pharmacology/Toxicology ; Phenotypes ; Proteins ; Proteomics ; Reagents ; Spectrometry ; Therapeutic targets ; Tobacco ; Transformed cells ; Ubiquitin ; Ubiquitin Thiolesterase - genetics</subject><ispartof>Cell biology and toxicology, 2021-08, Vol.37 (4), p.497-513</ispartof><rights>Springer Nature B.V. 2020</rights><rights>2020. Springer Nature B.V.</rights><rights>Springer Nature B.V. 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-a041c67bb85378d04a283c946e40b8168b66f648bf7ec2848277544c94fec2c03</citedby><cites>FETCH-LOGICAL-c419t-a041c67bb85378d04a283c946e40b8168b66f648bf7ec2848277544c94fec2c03</cites><orcidid>0000-0002-9533-020X ; 0000-0002-8515-2614 ; 0000-0003-1141-7234 ; 0000-0002-0570-2656 ; 0000-0002-7416-2788 ; 0000-0002-7146-7789 ; 0000-0003-1124-0045 ; 0000-0002-6732-8903 ; 0000-0002-6013-2190</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10565-020-09560-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10565-020-09560-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33040242$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Dan-Dan</creatorcontrib><creatorcontrib>Xu, Yan-Ming</creatorcontrib><creatorcontrib>Chen, De-Ju</creatorcontrib><creatorcontrib>Liang, Zhan-Ling</creatorcontrib><creatorcontrib>Chen, Xu-Li</creatorcontrib><creatorcontrib>Hylkema, Machteld N.</creatorcontrib><creatorcontrib>Rots, Marianne G.</creatorcontrib><creatorcontrib>Li, Sheng-Qing</creatorcontrib><creatorcontrib>Lau, Andy T. Y.</creatorcontrib><title>Ubiquitin carboxyl-terminal hydrolase isozyme L1/UCHL1 suppresses epithelial–mesenchymal transition and is under-expressed in cadmium-transformed human bronchial epithelial cells</title><title>Cell biology and toxicology</title><addtitle>Cell Biol Toxicol</addtitle><addtitle>Cell Biol Toxicol</addtitle><description>Cadmium (Cd), a highly toxic heavy metal, is widespreadly distributed in the environment. Chronic exposure to Cd is associated with the development of several diseases including cancers. Over the decade, many researches have been carried on various models to examine the acute effects of Cd; yet, limited knowledge is known about the long-term Cd exposure, especially in the human lung cells. Previously, we showed that chronic Cd-exposed human bronchial epithelial BEAS-2B cells exhibited transformed cell properties, such as anchorage-independent growth, augmented cell migration, and epithelial–mesenchymal transition (EMT). To study these Cd-transformed cells more comprehensively, here, we further characterized their subproteomes. Overall, a total of 63 differentially expressed proteins between Cd-transformed and passage-matched control cells among the five subcellular fractions (cytoplasmic, membrane, nuclear-soluble, chromatin-bound, and cytoskeletal) were identified by mass spectrometric analysis and database searching. Interestingly, we found that the thiol protease ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) is one of the severely downregulated proteins in the Cd-transformed cells. Notably, the EMT phenotype of Cd-transformed cells can be suppressed by forced ectopic expression of UCHL1, suggesting UCHL1 as a crucial modulator in the maintenance of the proper differentiation status in lung epithelial cells. Since EMT is considered as a critical step during malignant cell transformation, finding novel cellular targets that can antagonize this transition may lead to more efficient strategies to inhibit cancer development. Our data report for the first time that UCHL1 may play a function in the suppression of EMT in Cd-transformed human lung epithelial cells, indicating that UCHL1 might be a new therapeutic target for chronic Cd-induced carcinogenesis.
Graphical abstract</description><subject>Acute effects</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Cadmium</subject><subject>Cadmium - toxicity</subject><subject>Cancer</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Cell adhesion & migration</subject><subject>Cell Biology</subject><subject>Cell differentiation</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Chromatin</subject><subject>Chronic exposure</subject><subject>Cytoplasmic membranes</subject><subject>Cytoskeleton</subject><subject>Database searching</subject><subject>DNA methylation</subject><subject>Ectopic expression</subject><subject>Epithelial Cells</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Epithelium</subject><subject>Exposure</subject><subject>Gene expression</subject><subject>Heavy metals</subject><subject>Humans</subject><subject>Hydrolase</subject><subject>Life Sciences</subject><subject>Lungs</subject><subject>Mesenchyme</subject><subject>Original Article</subject><subject>Pharmacology/Toxicology</subject><subject>Phenotypes</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Reagents</subject><subject>Spectrometry</subject><subject>Therapeutic targets</subject><subject>Tobacco</subject><subject>Transformed cells</subject><subject>Ubiquitin</subject><subject>Ubiquitin Thiolesterase - genetics</subject><issn>0742-2091</issn><issn>1573-6822</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU2O1DAQhS0EYpqBC7BAllibKf_EcZaoBQxSS2zoteU4Dp1REmdciTRhxR24CifiJLgnw8-KleXye99T-RHyksMbDlBeIYdCFwwEMKgKDUw8IjtelJJpI8RjsoNSCSag4hfkGeINAGheFk_JhZSgQCixIz-OdXe7dHM3Uu9SHe_Wns0hDd3oenpamxR7h4F2GL-uQ6AHfnXcXx84xWWaUkAMSMPUzafQd67_-e37EDCM_rQO2T4nN2JGx5G6sckMuoxNSCzcbdY8Oqc2Q7cM7F7cxjTk8WkZ3EjrFDMpY_9JoD70PT4nT1rXY3jxcF6S4_t3n_fX7PDpw8f92wPzilczc6C412Vdm0KWpgHlhJG-UjooqA3Xpta61crUbRm8MMqIsiyUyoo23z3IS_J6404p3i4BZ3sTl5R_Bq0otKyk1OKsEpvKp4iYQmun1A0urZaDPRdlt6JsLsreF2VFNr16QC91XvmP5XczWSA3Aean8UtIf7P_g_0FHgmjjw</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Wu, Dan-Dan</creator><creator>Xu, Yan-Ming</creator><creator>Chen, De-Ju</creator><creator>Liang, Zhan-Ling</creator><creator>Chen, Xu-Li</creator><creator>Hylkema, Machteld N.</creator><creator>Rots, Marianne G.</creator><creator>Li, Sheng-Qing</creator><creator>Lau, Andy T. 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Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-a041c67bb85378d04a283c946e40b8168b66f648bf7ec2848277544c94fec2c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acute effects</topic><topic>Biochemistry</topic><topic>Biology</topic><topic>Biomedical and Life Sciences</topic><topic>Cadmium</topic><topic>Cadmium - toxicity</topic><topic>Cancer</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Cell adhesion & migration</topic><topic>Cell Biology</topic><topic>Cell differentiation</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Chromatin</topic><topic>Chronic exposure</topic><topic>Cytoplasmic membranes</topic><topic>Cytoskeleton</topic><topic>Database searching</topic><topic>DNA methylation</topic><topic>Ectopic expression</topic><topic>Epithelial Cells</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Epithelium</topic><topic>Exposure</topic><topic>Gene expression</topic><topic>Heavy metals</topic><topic>Humans</topic><topic>Hydrolase</topic><topic>Life Sciences</topic><topic>Lungs</topic><topic>Mesenchyme</topic><topic>Original Article</topic><topic>Pharmacology/Toxicology</topic><topic>Phenotypes</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Reagents</topic><topic>Spectrometry</topic><topic>Therapeutic targets</topic><topic>Tobacco</topic><topic>Transformed cells</topic><topic>Ubiquitin</topic><topic>Ubiquitin Thiolesterase - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Dan-Dan</creatorcontrib><creatorcontrib>Xu, Yan-Ming</creatorcontrib><creatorcontrib>Chen, De-Ju</creatorcontrib><creatorcontrib>Liang, Zhan-Ling</creatorcontrib><creatorcontrib>Chen, Xu-Li</creatorcontrib><creatorcontrib>Hylkema, Machteld N.</creatorcontrib><creatorcontrib>Rots, Marianne G.</creatorcontrib><creatorcontrib>Li, Sheng-Qing</creatorcontrib><creatorcontrib>Lau, Andy T. 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Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ubiquitin carboxyl-terminal hydrolase isozyme L1/UCHL1 suppresses epithelial–mesenchymal transition and is under-expressed in cadmium-transformed human bronchial epithelial cells</atitle><jtitle>Cell biology and toxicology</jtitle><stitle>Cell Biol Toxicol</stitle><addtitle>Cell Biol Toxicol</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>37</volume><issue>4</issue><spage>497</spage><epage>513</epage><pages>497-513</pages><issn>0742-2091</issn><eissn>1573-6822</eissn><abstract>Cadmium (Cd), a highly toxic heavy metal, is widespreadly distributed in the environment. Chronic exposure to Cd is associated with the development of several diseases including cancers. Over the decade, many researches have been carried on various models to examine the acute effects of Cd; yet, limited knowledge is known about the long-term Cd exposure, especially in the human lung cells. Previously, we showed that chronic Cd-exposed human bronchial epithelial BEAS-2B cells exhibited transformed cell properties, such as anchorage-independent growth, augmented cell migration, and epithelial–mesenchymal transition (EMT). To study these Cd-transformed cells more comprehensively, here, we further characterized their subproteomes. Overall, a total of 63 differentially expressed proteins between Cd-transformed and passage-matched control cells among the five subcellular fractions (cytoplasmic, membrane, nuclear-soluble, chromatin-bound, and cytoskeletal) were identified by mass spectrometric analysis and database searching. Interestingly, we found that the thiol protease ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) is one of the severely downregulated proteins in the Cd-transformed cells. Notably, the EMT phenotype of Cd-transformed cells can be suppressed by forced ectopic expression of UCHL1, suggesting UCHL1 as a crucial modulator in the maintenance of the proper differentiation status in lung epithelial cells. Since EMT is considered as a critical step during malignant cell transformation, finding novel cellular targets that can antagonize this transition may lead to more efficient strategies to inhibit cancer development. Our data report for the first time that UCHL1 may play a function in the suppression of EMT in Cd-transformed human lung epithelial cells, indicating that UCHL1 might be a new therapeutic target for chronic Cd-induced carcinogenesis.
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| fulltext | fulltext |
| identifier | ISSN: 0742-2091 |
| ispartof | Cell biology and toxicology, 2021-08, Vol.37 (4), p.497-513 |
| issn | 0742-2091 1573-6822 |
| language | eng |
| recordid | cdi_proquest_journals_2563933620 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Acute effects Biochemistry Biology Biomedical and Life Sciences Cadmium Cadmium - toxicity Cancer Carcinogenesis Carcinogens Cell adhesion & migration Cell Biology Cell differentiation Cell migration Cell Movement Chromatin Chronic exposure Cytoplasmic membranes Cytoskeleton Database searching DNA methylation Ectopic expression Epithelial Cells Epithelial-Mesenchymal Transition Epithelium Exposure Gene expression Heavy metals Humans Hydrolase Life Sciences Lungs Mesenchyme Original Article Pharmacology/Toxicology Phenotypes Proteins Proteomics Reagents Spectrometry Therapeutic targets Tobacco Transformed cells Ubiquitin Ubiquitin Thiolesterase - genetics |
| title | Ubiquitin carboxyl-terminal hydrolase isozyme L1/UCHL1 suppresses epithelial–mesenchymal transition and is under-expressed in cadmium-transformed human bronchial epithelial cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T13%3A09%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ubiquitin%20carboxyl-terminal%20hydrolase%20isozyme%20L1/UCHL1%20suppresses%20epithelial%E2%80%93mesenchymal%20transition%20and%20is%20under-expressed%20in%20cadmium-transformed%20human%20bronchial%20epithelial%20cells&rft.jtitle=Cell%20biology%20and%20toxicology&rft.au=Wu,%20Dan-Dan&rft.date=2021-08-01&rft.volume=37&rft.issue=4&rft.spage=497&rft.epage=513&rft.pages=497-513&rft.issn=0742-2091&rft.eissn=1573-6822&rft_id=info:doi/10.1007/s10565-020-09560-2&rft_dat=%3Cproquest_cross%3E2563933620%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2563933620&rft_id=info:pmid/33040242&rfr_iscdi=true |