Epithelial to Mesenchymal Transition Regulates Surface PD-L1 via CMTM6 and CMTM7 Induction in Breast Cancer
CMTM6 is a critical regulator of cell surface expression of PD-L1 in tumor cells, but little is known about the transcriptional regulation of CMTM6. Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines...
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description | CMTM6 is a critical regulator of cell surface expression of PD-L1 in tumor cells, but little is known about the transcriptional regulation of CMTM6. Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines and with the major EMT marker Vimentin in triple-negative breast cancers (TNBC). We showed that CMTM6 is concomitantly overexpressed with PD-L1 in breast mesenchymal compared with the epithelial cells. Driving a mesenchymal phenotype in SNAI1-inducible MCF-7 cells (MCF-7
cells) increased both PD-L1 and CMTM6. CMTM6 silencing in MCF-7
cells partially reduced cell surface expression of PD-L1, indicating that a proportion of the PD-L1 on the surface of MCF-7
cells depends on CMTM6. We also found a positive correlation between CMTM3 and CMTM7 expression with EMT score in breast cancer cells, and with Vimentin in TNBC patients. Dual knockdown of CMTM6 and CMTM7 significantly decreased PD-L1 surface expression in MCF-7
cells, indicating that both CMTM6 and CMTM7 regulate the expression of PD-L1. This study highlights the importance of CMTM6 and CMTM7 in EMT-induced PD-L1 and suggests that EMT, CMTM6 or CMTM7 modulators can be combined with anti-PD-L1 in patients with highly aggressive breast cancer. |
doi_str_mv | 10.3390/cancers13051165 |
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cells) increased both PD-L1 and CMTM6. CMTM6 silencing in MCF-7
cells partially reduced cell surface expression of PD-L1, indicating that a proportion of the PD-L1 on the surface of MCF-7
cells depends on CMTM6. We also found a positive correlation between CMTM3 and CMTM7 expression with EMT score in breast cancer cells, and with Vimentin in TNBC patients. Dual knockdown of CMTM6 and CMTM7 significantly decreased PD-L1 surface expression in MCF-7
cells, indicating that both CMTM6 and CMTM7 regulate the expression of PD-L1. This study highlights the importance of CMTM6 and CMTM7 in EMT-induced PD-L1 and suggests that EMT, CMTM6 or CMTM7 modulators can be combined with anti-PD-L1 in patients with highly aggressive breast cancer.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13051165</identifier><identifier>PMID: 33803139</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antibodies ; Breast cancer ; Cell surface ; Chromosomes ; Correlation analysis ; Epithelial cells ; Flow cytometry ; Gene regulation ; Genotype & phenotype ; Human health sciences ; Mesenchyme ; Oncologie ; Oncology ; PD-L1 protein ; Phenotypes ; Proteins ; Sciences de la santé humaine ; Snail protein ; Software ; Transcription ; Tumor cell lines ; Tumor cells ; Vimentin</subject><ispartof>Cancers, 2021-03, Vol.13 (5), p.1165</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-d88f98106236585b370c3f42fb3e636e74b25b27e15601d15f1810b10bbab0903</citedby><cites>FETCH-LOGICAL-c465t-d88f98106236585b370c3f42fb3e636e74b25b27e15601d15f1810b10bbab0903</cites><orcidid>0000-0002-4157-6538 ; 0000-0003-0157-2257 ; 0000-0002-9763-0943 ; 0000-0001-6624-1593</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963182/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963182/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33803139$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiao, Malina</creatorcontrib><creatorcontrib>Hasmim, Meriem</creatorcontrib><creatorcontrib>Lequeux, Audrey</creatorcontrib><creatorcontrib>Moer, Kris Van</creatorcontrib><creatorcontrib>Tan, Tuan Zea</creatorcontrib><creatorcontrib>Gilles, Christine</creatorcontrib><creatorcontrib>Hollier, Brett G</creatorcontrib><creatorcontrib>Thiery, Jean Paul</creatorcontrib><creatorcontrib>Berchem, Guy</creatorcontrib><creatorcontrib>Janji, Bassam</creatorcontrib><creatorcontrib>Noman, Muhammad Zaeem</creatorcontrib><title>Epithelial to Mesenchymal Transition Regulates Surface PD-L1 via CMTM6 and CMTM7 Induction in Breast Cancer</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>CMTM6 is a critical regulator of cell surface expression of PD-L1 in tumor cells, but little is known about the transcriptional regulation of CMTM6. Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines and with the major EMT marker Vimentin in triple-negative breast cancers (TNBC). We showed that CMTM6 is concomitantly overexpressed with PD-L1 in breast mesenchymal compared with the epithelial cells. Driving a mesenchymal phenotype in SNAI1-inducible MCF-7 cells (MCF-7
cells) increased both PD-L1 and CMTM6. CMTM6 silencing in MCF-7
cells partially reduced cell surface expression of PD-L1, indicating that a proportion of the PD-L1 on the surface of MCF-7
cells depends on CMTM6. We also found a positive correlation between CMTM3 and CMTM7 expression with EMT score in breast cancer cells, and with Vimentin in TNBC patients. Dual knockdown of CMTM6 and CMTM7 significantly decreased PD-L1 surface expression in MCF-7
cells, indicating that both CMTM6 and CMTM7 regulate the expression of PD-L1. 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Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines and with the major EMT marker Vimentin in triple-negative breast cancers (TNBC). We showed that CMTM6 is concomitantly overexpressed with PD-L1 in breast mesenchymal compared with the epithelial cells. Driving a mesenchymal phenotype in SNAI1-inducible MCF-7 cells (MCF-7
cells) increased both PD-L1 and CMTM6. CMTM6 silencing in MCF-7
cells partially reduced cell surface expression of PD-L1, indicating that a proportion of the PD-L1 on the surface of MCF-7
cells depends on CMTM6. We also found a positive correlation between CMTM3 and CMTM7 expression with EMT score in breast cancer cells, and with Vimentin in TNBC patients. Dual knockdown of CMTM6 and CMTM7 significantly decreased PD-L1 surface expression in MCF-7
cells, indicating that both CMTM6 and CMTM7 regulate the expression of PD-L1. This study highlights the importance of CMTM6 and CMTM7 in EMT-induced PD-L1 and suggests that EMT, CMTM6 or CMTM7 modulators can be combined with anti-PD-L1 in patients with highly aggressive breast cancer.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33803139</pmid><doi>10.3390/cancers13051165</doi><orcidid>https://orcid.org/0000-0002-4157-6538</orcidid><orcidid>https://orcid.org/0000-0003-0157-2257</orcidid><orcidid>https://orcid.org/0000-0002-9763-0943</orcidid><orcidid>https://orcid.org/0000-0001-6624-1593</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antibodies Breast cancer Cell surface Chromosomes Correlation analysis Epithelial cells Flow cytometry Gene regulation Genotype & phenotype Human health sciences Mesenchyme Oncologie Oncology PD-L1 protein Phenotypes Proteins Sciences de la santé humaine Snail protein Software Transcription Tumor cell lines Tumor cells Vimentin |
title | Epithelial to Mesenchymal Transition Regulates Surface PD-L1 via CMTM6 and CMTM7 Induction in Breast Cancer |
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