SPOCK1 Is a Novel Transforming Growth Factor-β-Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer
In addition to contraction, myoepithelia have diverse paracrine effects, including a tumor suppression effect. However, certain myoepithelial markers have been shown to contribute to tumor progression. Transforming growth factor-β (TGF-β) is involved in the transdifferentiation of fibroblasts to con...
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| description | In addition to contraction, myoepithelia have diverse paracrine effects, including a tumor suppression effect. However, certain myoepithelial markers have been shown to contribute to tumor progression. Transforming growth factor-β (TGF-β) is involved in the transdifferentiation of fibroblasts to contractile myofibroblasts. We investigated whether TGF-β can upregulate potential myoepithelial markers, which may have functional and clinicopathological significance in breast cancer. We found that TGF-β induced SPOCK1 expression in MCF10A, MCF12A, and M10 breast cells and demonstrated SPOCK1 as a novel myoepithelial marker that was immunolocalized within or beneath myoepithelia lining ductolobular units. A functional study showed that overexpression of SPOCK1 enhanced invasiveness in mammary immortalized and cancer cells. To further determine the biological significance of SPOCK1 in breast cancer, we investigated the expression of SPOCK1 in 478 invasive ductal carcinoma (IDC) cases through immunohistochemistry and correlated the expression with clinicopathological characteristics. SPOCK1 expression was significantly correlated with high pathological tumor size (P = 0.012), high histological grade (P = 0.013), the triple-negative phenotype (P = 0.022), and the basal-like phenotype (P = 0.026) and was correlated with a significantly poorer overall survival on univariate analysis (P = 0.001, log-rank test). Multivariate Cox regression analysis demonstrated that SPOCK1 expression maintained an independent poor prognostic factor of overall survival. Analysis of SPOCK1 expression on various non-IDC carcinoma subtypes showed an enrichment of SPOCK1 expression in metaplastic carcinoma, which is pathogenetically closely related to epithelial-mesenchymal transition (EMT). In conclusion, we identified SPOCK1 as a novel TGF-β-induced myoepithelial marker and further demonstrated that SPOCK1 enhanced invasion in breast cancer cells and correlated with poor prognosis in breast cancer clinical samples. The enrichment of SPOCK1 expression in metaplastic carcinoma and the correlation between SPOCK1 expression and high histological grading and basal-like phenotypes in IDC evidence an association between SPOCK1 and EMT. |
| doi_str_mv | 10.1371/journal.pone.0162933 |
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However, certain myoepithelial markers have been shown to contribute to tumor progression. Transforming growth factor-β (TGF-β) is involved in the transdifferentiation of fibroblasts to contractile myofibroblasts. We investigated whether TGF-β can upregulate potential myoepithelial markers, which may have functional and clinicopathological significance in breast cancer. We found that TGF-β induced SPOCK1 expression in MCF10A, MCF12A, and M10 breast cells and demonstrated SPOCK1 as a novel myoepithelial marker that was immunolocalized within or beneath myoepithelia lining ductolobular units. A functional study showed that overexpression of SPOCK1 enhanced invasiveness in mammary immortalized and cancer cells. To further determine the biological significance of SPOCK1 in breast cancer, we investigated the expression of SPOCK1 in 478 invasive ductal carcinoma (IDC) cases through immunohistochemistry and correlated the expression with clinicopathological characteristics. SPOCK1 expression was significantly correlated with high pathological tumor size (P = 0.012), high histological grade (P = 0.013), the triple-negative phenotype (P = 0.022), and the basal-like phenotype (P = 0.026) and was correlated with a significantly poorer overall survival on univariate analysis (P = 0.001, log-rank test). Multivariate Cox regression analysis demonstrated that SPOCK1 expression maintained an independent poor prognostic factor of overall survival. Analysis of SPOCK1 expression on various non-IDC carcinoma subtypes showed an enrichment of SPOCK1 expression in metaplastic carcinoma, which is pathogenetically closely related to epithelial-mesenchymal transition (EMT). In conclusion, we identified SPOCK1 as a novel TGF-β-induced myoepithelial marker and further demonstrated that SPOCK1 enhanced invasion in breast cancer cells and correlated with poor prognosis in breast cancer clinical samples. The enrichment of SPOCK1 expression in metaplastic carcinoma and the correlation between SPOCK1 expression and high histological grading and basal-like phenotypes in IDC evidence an association between SPOCK1 and EMT.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0162933</identifier><identifier>PMID: 27626636</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology and Life Sciences ; Biomarkers, Tumor - metabolism ; Blotting, Western ; Breast cancer ; Breast Neoplasms - diagnosis ; Breast Neoplasms - pathology ; Cancer ; Carcinoma, Ductal, Breast - diagnosis ; Carcinoma, Ductal, Breast - pathology ; Cell growth ; Cell Line, Tumor ; Contractility ; Contraction ; Enrichment ; Epithelial-Mesenchymal Transition - physiology ; Extracellular matrix ; Female ; Fibroblasts ; Gene expression ; Genotype & phenotype ; Growth factors ; Humans ; Immunohistochemistry ; Invasiveness ; Kaplan-Meier Estimate ; Kidney diseases ; Markers ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Mesenchyme ; Middle Aged ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; Paracrine signalling ; Pathology ; Prognosis ; Proportional Hazards Models ; Proteoglycans - physiology ; Regression analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Smooth muscle ; Survival ; Survival Analysis ; Transforming Growth Factor beta - physiology ; Transforming growth factor-a ; Transforming growth factor-b ; Tumor suppression ; Tumors ; Wound healing</subject><ispartof>PloS one, 2016-09, Vol.11 (9), p.e0162933-e0162933</ispartof><rights>2016 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Fan et al 2016 Fan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-73728556e698dea7bf85e1aac05ee201dfb1f0319d66420f3af3f17539e72e6b3</citedby><cites>FETCH-LOGICAL-c526t-73728556e698dea7bf85e1aac05ee201dfb1f0319d66420f3af3f17539e72e6b3</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/PMC5023187/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023187/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27626636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Castresana, Javier S</contributor><creatorcontrib>Fan, Li-Ching</creatorcontrib><creatorcontrib>Jeng, Yung-Ming</creatorcontrib><creatorcontrib>Lu, Yueh-Tong</creatorcontrib><creatorcontrib>Lien, Huang-Chun</creatorcontrib><title>SPOCK1 Is a Novel Transforming Growth Factor-β-Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In addition to contraction, myoepithelia have diverse paracrine effects, including a tumor suppression effect. However, certain myoepithelial markers have been shown to contribute to tumor progression. Transforming growth factor-β (TGF-β) is involved in the transdifferentiation of fibroblasts to contractile myofibroblasts. We investigated whether TGF-β can upregulate potential myoepithelial markers, which may have functional and clinicopathological significance in breast cancer. We found that TGF-β induced SPOCK1 expression in MCF10A, MCF12A, and M10 breast cells and demonstrated SPOCK1 as a novel myoepithelial marker that was immunolocalized within or beneath myoepithelia lining ductolobular units. A functional study showed that overexpression of SPOCK1 enhanced invasiveness in mammary immortalized and cancer cells. To further determine the biological significance of SPOCK1 in breast cancer, we investigated the expression of SPOCK1 in 478 invasive ductal carcinoma (IDC) cases through immunohistochemistry and correlated the expression with clinicopathological characteristics. 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The enrichment of SPOCK1 expression in metaplastic carcinoma and the correlation between SPOCK1 expression and high histological grading and basal-like phenotypes in IDC evidence an association between SPOCK1 and EMT.</description><subject>Biology and Life Sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Blotting, Western</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Carcinoma, Ductal, Breast - diagnosis</subject><subject>Carcinoma, Ductal, Breast - pathology</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Contractility</subject><subject>Contraction</subject><subject>Enrichment</subject><subject>Epithelial-Mesenchymal Transition - physiology</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Genotype & phenotype</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Invasiveness</subject><subject>Kaplan-Meier Estimate</subject><subject>Kidney diseases</subject><subject>Markers</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchyme</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Paracrine signalling</subject><subject>Pathology</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Proteoglycans - physiology</subject><subject>Regression analysis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Smooth muscle</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Transforming Growth Factor beta - physiology</subject><subject>Transforming growth factor-a</subject><subject>Transforming growth factor-b</subject><subject>Tumor suppression</subject><subject>Tumors</subject><subject>Wound healing</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</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><sourceid>DOA</sourceid><recordid>eNptkt1uEzEQhVcIREvhDRBY4oabDf7J2rs3SLBqS0RLIxGurVnvONng2MHepOqT8B48CM_EhqRVi7iyNXO-4xnrZNlLRkdMKPZuGTbRgxutg8cRZZJXQjzKjlkleC45FY_v3Y-yZyktKS1EKeXT7IgryaUU8jj7-XV6VX9mZJIIkC9hi47MIvhkQ1x1fk7OY7juF-QMTB9i_vtXPvHtxmBLLm8Crrt-ga4DRy4hfsdIZgvoyalfgDeYyMRvIXXBE_AtqUOM6KAf6tcDRqYhRDKNYe5D6hLpPPkYEVJP6h0cn2dPLLiELw7nSfbt7HRWf8ovrs4n9YeL3BRc9rkSipdFIVFWZYugGlsWyAAMLRA5Za1tmKWCVa2UY06tACssU4WoUHGUjTjJXu991y4kffjTpFnJqjEvleKDYrJXtAGWeh27FcQbHaDTfwshzjXEvjMOtWoNQ2ysYGDGKExpG2GrMVWVQDk0Bq_3h9c2zQpbg76P4B6YPuz4bqHnYasLygUr1WDw9mAQw48Npl6vumTQOfAYNru5OS0qwagYpG_-kf5_u_FeZWJIKaK9G4ZRvcvZLaV3OdOHnA3Yq_uL3EG3wRJ_AHRw0_c</recordid><startdate>20160914</startdate><enddate>20160914</enddate><creator>Fan, Li-Ching</creator><creator>Jeng, Yung-Ming</creator><creator>Lu, Yueh-Tong</creator><creator>Lien, Huang-Chun</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160914</creationdate><title>SPOCK1 Is a Novel Transforming Growth Factor-β-Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer</title><author>Fan, Li-Ching ; Jeng, Yung-Ming ; Lu, Yueh-Tong ; Lien, Huang-Chun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-73728556e698dea7bf85e1aac05ee201dfb1f0319d66420f3af3f17539e72e6b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Biology and Life Sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Blotting, Western</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - diagnosis</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Carcinoma, Ductal, Breast - diagnosis</topic><topic>Carcinoma, Ductal, Breast - pathology</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Contractility</topic><topic>Contraction</topic><topic>Enrichment</topic><topic>Epithelial-Mesenchymal Transition - physiology</topic><topic>Extracellular matrix</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Genotype & phenotype</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Invasiveness</topic><topic>Kaplan-Meier Estimate</topic><topic>Kidney diseases</topic><topic>Markers</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchyme</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Paracrine signalling</topic><topic>Pathology</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Proteoglycans - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fan, Li-Ching</au><au>Jeng, Yung-Ming</au><au>Lu, Yueh-Tong</au><au>Lien, Huang-Chun</au><au>Castresana, Javier S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SPOCK1 Is a Novel Transforming Growth Factor-β-Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-09-14</date><risdate>2016</risdate><volume>11</volume><issue>9</issue><spage>e0162933</spage><epage>e0162933</epage><pages>e0162933-e0162933</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In addition to contraction, myoepithelia have diverse paracrine effects, including a tumor suppression effect. However, certain myoepithelial markers have been shown to contribute to tumor progression. Transforming growth factor-β (TGF-β) is involved in the transdifferentiation of fibroblasts to contractile myofibroblasts. We investigated whether TGF-β can upregulate potential myoepithelial markers, which may have functional and clinicopathological significance in breast cancer. We found that TGF-β induced SPOCK1 expression in MCF10A, MCF12A, and M10 breast cells and demonstrated SPOCK1 as a novel myoepithelial marker that was immunolocalized within or beneath myoepithelia lining ductolobular units. A functional study showed that overexpression of SPOCK1 enhanced invasiveness in mammary immortalized and cancer cells. To further determine the biological significance of SPOCK1 in breast cancer, we investigated the expression of SPOCK1 in 478 invasive ductal carcinoma (IDC) cases through immunohistochemistry and correlated the expression with clinicopathological characteristics. SPOCK1 expression was significantly correlated with high pathological tumor size (P = 0.012), high histological grade (P = 0.013), the triple-negative phenotype (P = 0.022), and the basal-like phenotype (P = 0.026) and was correlated with a significantly poorer overall survival on univariate analysis (P = 0.001, log-rank test). Multivariate Cox regression analysis demonstrated that SPOCK1 expression maintained an independent poor prognostic factor of overall survival. Analysis of SPOCK1 expression on various non-IDC carcinoma subtypes showed an enrichment of SPOCK1 expression in metaplastic carcinoma, which is pathogenetically closely related to epithelial-mesenchymal transition (EMT). In conclusion, we identified SPOCK1 as a novel TGF-β-induced myoepithelial marker and further demonstrated that SPOCK1 enhanced invasion in breast cancer cells and correlated with poor prognosis in breast cancer clinical samples. The enrichment of SPOCK1 expression in metaplastic carcinoma and the correlation between SPOCK1 expression and high histological grading and basal-like phenotypes in IDC evidence an association between SPOCK1 and EMT.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27626636</pmid><doi>10.1371/journal.pone.0162933</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1819428772 |
| source | PubMed Central database; MEDLINE; Public Library of Science（OA）; Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Biology and Life Sciences Biomarkers, Tumor - metabolism Blotting, Western Breast cancer Breast Neoplasms - diagnosis Breast Neoplasms - pathology Cancer Carcinoma, Ductal, Breast - diagnosis Carcinoma, Ductal, Breast - pathology Cell growth Cell Line, Tumor Contractility Contraction Enrichment Epithelial-Mesenchymal Transition - physiology Extracellular matrix Female Fibroblasts Gene expression Genotype & phenotype Growth factors Humans Immunohistochemistry Invasiveness Kaplan-Meier Estimate Kidney diseases Markers Medical prognosis Medicine Medicine and Health Sciences Mesenchyme Middle Aged Neoplasm Invasiveness Oligonucleotide Array Sequence Analysis Paracrine signalling Pathology Prognosis Proportional Hazards Models Proteoglycans - physiology Regression analysis Reverse Transcriptase Polymerase Chain Reaction Smooth muscle Survival Survival Analysis Transforming Growth Factor beta - physiology Transforming growth factor-a Transforming growth factor-b Tumor suppression Tumors Wound healing |
| title | SPOCK1 Is a Novel Transforming Growth Factor-β-Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T05%3A04%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=SPOCK1%20Is%20a%20Novel%20Transforming%20Growth%20Factor-%CE%B2-Induced%20Myoepithelial%20Marker%20That%20Enhances%20Invasion%20and%20Correlates%20with%20Poor%20Prognosis%20in%20Breast%20Cancer&rft.jtitle=PloS%20one&rft.au=Fan,%20Li-Ching&rft.date=2016-09-14&rft.volume=11&rft.issue=9&rft.spage=e0162933&rft.epage=e0162933&rft.pages=e0162933-e0162933&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0162933&rft_dat=%3Cproquest_plos_%3E4181963661%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1819428772&rft_id=info:pmid/27626636&rft_doaj_id=oai_doaj_org_article_7dc1eebf31ac4e3c8fb3f940793e6eeb&rfr_iscdi=true |