SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin
The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that th...
Gespeichert in:
| Veröffentlicht in: | Science signaling 2020-10, Vol.13 (654) |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 654 |
| container_start_page | |
| container_title | Science signaling |
| container_volume | 13 |
| creator | Bhattacharya, Apoorva Mukherjee, Shravanti Khan, Poulami Banerjee, Shruti Dutta, Apratim Banerjee, Nilanjan Sengupta, Debomita Basak, Udit Chakraborty, Sourio Dutta, Abhishek Chattopadhyay, Samit Jana, Kuladip Sarkar, Diptendra K Chatterjee, Subhrangsu Das, Tanya |
| description | The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that the expression of
was decreased in CSCs through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1. Overexpressing SMAR1 sensitized CSCs to chemotherapy through SMAR1-dependent recruitment of HDAC2 to the promoter of the gene encoding the drug efflux pump ABCG2. Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored
expression and
repression and enhanced tumor sensitivity to doxorubicin. Our findings reveal transcriptional mechanisms regulating
that also regulate cancer stemness and chemoresistance and suggest that, by restoring
expression, aspirin might enhance chemotherapeutic efficacy in patients with stem-like tumors. |
| doi_str_mv | 10.1126/scisignal.aay6077 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2452979562</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2452979562</sourcerecordid><originalsourceid>FETCH-LOGICAL-c329t-654f03452f85df3bc4c6bd6fba8958ea20f72a2b437dedea6a1ed0a9c29648e43</originalsourceid><addsrcrecordid>eNpdkctu1jAQha0KRK8PwAZZYsMmxZfEiZdVVdpKrZC4rKOJMykuiR08CdK_4tVx6N8uWNnWfOfMjA9jb6U4l1KZj-Q8-YcA4znAzoi6PmBH0uq6sLKsXm33sipEU9eH7JjoUQgjlbJv2KHWolGqaY7Yn6_3F18kTzgnJPIx8G7H53FNfo4LBrfjA7glJuIQeu5iIPy1Yli4-4FTzBpPCwSH3GdlQqBc2d6J04JTMfqfyB2OI3FPuctvTIT91gNo9smHU_Z6gJHwbH-esO-frr5d3hR3n69vLy_uCqeVXQpTlYPQZaWGpuoH3bnSma43QweNrRoEJYZagepKXffYIxiQ2AuwTllTNljqE_bhyXdOMS9ASzt52gaDgHGlVmVvW9vKqIy-_w99jGvKv_yP0hmyWmdKPlEuRaKEQzsnP0HatVK0WzrtSzrtPp2sebd3XrsJ-xfFcxz6L8g6kTU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2453795933</pqid></control><display><type>article</type><title>SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin</title><source>American Association for the Advancement of Science</source><creator>Bhattacharya, Apoorva ; Mukherjee, Shravanti ; Khan, Poulami ; Banerjee, Shruti ; Dutta, Apratim ; Banerjee, Nilanjan ; Sengupta, Debomita ; Basak, Udit ; Chakraborty, Sourio ; Dutta, Abhishek ; Chattopadhyay, Samit ; Jana, Kuladip ; Sarkar, Diptendra K ; Chatterjee, Subhrangsu ; Das, Tanya</creator><creatorcontrib>Bhattacharya, Apoorva ; Mukherjee, Shravanti ; Khan, Poulami ; Banerjee, Shruti ; Dutta, Apratim ; Banerjee, Nilanjan ; Sengupta, Debomita ; Basak, Udit ; Chakraborty, Sourio ; Dutta, Abhishek ; Chattopadhyay, Samit ; Jana, Kuladip ; Sarkar, Diptendra K ; Chatterjee, Subhrangsu ; Das, Tanya</creatorcontrib><description>The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that the expression of
was decreased in CSCs through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1. Overexpressing SMAR1 sensitized CSCs to chemotherapy through SMAR1-dependent recruitment of HDAC2 to the promoter of the gene encoding the drug efflux pump ABCG2. Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored
expression and
repression and enhanced tumor sensitivity to doxorubicin. Our findings reveal transcriptional mechanisms regulating
that also regulate cancer stemness and chemoresistance and suggest that, by restoring
expression, aspirin might enhance chemotherapeutic efficacy in patients with stem-like tumors.</description><identifier>ISSN: 1945-0877</identifier><identifier>EISSN: 1937-9145</identifier><identifier>DOI: 10.1126/scisignal.aay6077</identifier><identifier>PMID: 33082288</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Anti-inflammatory agents ; Aspirin ; Breast cancer ; Chemoresistance ; Chemotherapy ; Colorectal carcinoma ; Cytotoxicity ; Doxorubicin ; Efflux ; Gene silencing ; HDAC2 protein ; Histone deacetylase ; Inflammation ; Invasiveness ; Nonsteroidal anti-inflammatory drugs ; Oct-4 protein ; Pluripotency ; Sensitivity enhancement ; Stem cell transplantation ; Stem cells ; Toxicity ; Tumor cells ; Tumors</subject><ispartof>Science signaling, 2020-10, Vol.13 (654)</ispartof><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</rights><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c329t-654f03452f85df3bc4c6bd6fba8958ea20f72a2b437dedea6a1ed0a9c29648e43</citedby><cites>FETCH-LOGICAL-c329t-654f03452f85df3bc4c6bd6fba8958ea20f72a2b437dedea6a1ed0a9c29648e43</cites><orcidid>0000-0003-4748-253X ; 0000-0002-9643-5396 ; 0000-0002-9583-0693 ; 0000-0001-5016-8918</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2884,2885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33082288$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhattacharya, Apoorva</creatorcontrib><creatorcontrib>Mukherjee, Shravanti</creatorcontrib><creatorcontrib>Khan, Poulami</creatorcontrib><creatorcontrib>Banerjee, Shruti</creatorcontrib><creatorcontrib>Dutta, Apratim</creatorcontrib><creatorcontrib>Banerjee, Nilanjan</creatorcontrib><creatorcontrib>Sengupta, Debomita</creatorcontrib><creatorcontrib>Basak, Udit</creatorcontrib><creatorcontrib>Chakraborty, Sourio</creatorcontrib><creatorcontrib>Dutta, Abhishek</creatorcontrib><creatorcontrib>Chattopadhyay, Samit</creatorcontrib><creatorcontrib>Jana, Kuladip</creatorcontrib><creatorcontrib>Sarkar, Diptendra K</creatorcontrib><creatorcontrib>Chatterjee, Subhrangsu</creatorcontrib><creatorcontrib>Das, Tanya</creatorcontrib><title>SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin</title><title>Science signaling</title><addtitle>Sci Signal</addtitle><description>The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that the expression of
was decreased in CSCs through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1. Overexpressing SMAR1 sensitized CSCs to chemotherapy through SMAR1-dependent recruitment of HDAC2 to the promoter of the gene encoding the drug efflux pump ABCG2. Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored
expression and
repression and enhanced tumor sensitivity to doxorubicin. Our findings reveal transcriptional mechanisms regulating
that also regulate cancer stemness and chemoresistance and suggest that, by restoring
expression, aspirin might enhance chemotherapeutic efficacy in patients with stem-like tumors.</description><subject>Anti-inflammatory agents</subject><subject>Aspirin</subject><subject>Breast cancer</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Colorectal carcinoma</subject><subject>Cytotoxicity</subject><subject>Doxorubicin</subject><subject>Efflux</subject><subject>Gene silencing</subject><subject>HDAC2 protein</subject><subject>Histone deacetylase</subject><subject>Inflammation</subject><subject>Invasiveness</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Oct-4 protein</subject><subject>Pluripotency</subject><subject>Sensitivity enhancement</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Toxicity</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1945-0877</issn><issn>1937-9145</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpdkctu1jAQha0KRK8PwAZZYsMmxZfEiZdVVdpKrZC4rKOJMykuiR08CdK_4tVx6N8uWNnWfOfMjA9jb6U4l1KZj-Q8-YcA4znAzoi6PmBH0uq6sLKsXm33sipEU9eH7JjoUQgjlbJv2KHWolGqaY7Yn6_3F18kTzgnJPIx8G7H53FNfo4LBrfjA7glJuIQeu5iIPy1Yli4-4FTzBpPCwSH3GdlQqBc2d6J04JTMfqfyB2OI3FPuctvTIT91gNo9smHU_Z6gJHwbH-esO-frr5d3hR3n69vLy_uCqeVXQpTlYPQZaWGpuoH3bnSma43QweNrRoEJYZagepKXffYIxiQ2AuwTllTNljqE_bhyXdOMS9ASzt52gaDgHGlVmVvW9vKqIy-_w99jGvKv_yP0hmyWmdKPlEuRaKEQzsnP0HatVK0WzrtSzrtPp2sebd3XrsJ-xfFcxz6L8g6kTU</recordid><startdate>20201020</startdate><enddate>20201020</enddate><creator>Bhattacharya, Apoorva</creator><creator>Mukherjee, Shravanti</creator><creator>Khan, Poulami</creator><creator>Banerjee, Shruti</creator><creator>Dutta, Apratim</creator><creator>Banerjee, Nilanjan</creator><creator>Sengupta, Debomita</creator><creator>Basak, Udit</creator><creator>Chakraborty, Sourio</creator><creator>Dutta, Abhishek</creator><creator>Chattopadhyay, Samit</creator><creator>Jana, Kuladip</creator><creator>Sarkar, Diptendra K</creator><creator>Chatterjee, Subhrangsu</creator><creator>Das, Tanya</creator><general>The American Association for the Advancement of Science</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>JQ2</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4748-253X</orcidid><orcidid>https://orcid.org/0000-0002-9643-5396</orcidid><orcidid>https://orcid.org/0000-0002-9583-0693</orcidid><orcidid>https://orcid.org/0000-0001-5016-8918</orcidid></search><sort><creationdate>20201020</creationdate><title>SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin</title><author>Bhattacharya, Apoorva ; Mukherjee, Shravanti ; Khan, Poulami ; Banerjee, Shruti ; Dutta, Apratim ; Banerjee, Nilanjan ; Sengupta, Debomita ; Basak, Udit ; Chakraborty, Sourio ; Dutta, Abhishek ; Chattopadhyay, Samit ; Jana, Kuladip ; Sarkar, Diptendra K ; Chatterjee, Subhrangsu ; Das, Tanya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c329t-654f03452f85df3bc4c6bd6fba8958ea20f72a2b437dedea6a1ed0a9c29648e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anti-inflammatory agents</topic><topic>Aspirin</topic><topic>Breast cancer</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Colorectal carcinoma</topic><topic>Cytotoxicity</topic><topic>Doxorubicin</topic><topic>Efflux</topic><topic>Gene silencing</topic><topic>HDAC2 protein</topic><topic>Histone deacetylase</topic><topic>Inflammation</topic><topic>Invasiveness</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Oct-4 protein</topic><topic>Pluripotency</topic><topic>Sensitivity enhancement</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Toxicity</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bhattacharya, Apoorva</creatorcontrib><creatorcontrib>Mukherjee, Shravanti</creatorcontrib><creatorcontrib>Khan, Poulami</creatorcontrib><creatorcontrib>Banerjee, Shruti</creatorcontrib><creatorcontrib>Dutta, Apratim</creatorcontrib><creatorcontrib>Banerjee, Nilanjan</creatorcontrib><creatorcontrib>Sengupta, Debomita</creatorcontrib><creatorcontrib>Basak, Udit</creatorcontrib><creatorcontrib>Chakraborty, Sourio</creatorcontrib><creatorcontrib>Dutta, Abhishek</creatorcontrib><creatorcontrib>Chattopadhyay, Samit</creatorcontrib><creatorcontrib>Jana, Kuladip</creatorcontrib><creatorcontrib>Sarkar, Diptendra K</creatorcontrib><creatorcontrib>Chatterjee, Subhrangsu</creatorcontrib><creatorcontrib>Das, Tanya</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science signaling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bhattacharya, Apoorva</au><au>Mukherjee, Shravanti</au><au>Khan, Poulami</au><au>Banerjee, Shruti</au><au>Dutta, Apratim</au><au>Banerjee, Nilanjan</au><au>Sengupta, Debomita</au><au>Basak, Udit</au><au>Chakraborty, Sourio</au><au>Dutta, Abhishek</au><au>Chattopadhyay, Samit</au><au>Jana, Kuladip</au><au>Sarkar, Diptendra K</au><au>Chatterjee, Subhrangsu</au><au>Das, Tanya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin</atitle><jtitle>Science signaling</jtitle><addtitle>Sci Signal</addtitle><date>2020-10-20</date><risdate>2020</risdate><volume>13</volume><issue>654</issue><issn>1945-0877</issn><eissn>1937-9145</eissn><abstract>The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that the expression of
was decreased in CSCs through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1. Overexpressing SMAR1 sensitized CSCs to chemotherapy through SMAR1-dependent recruitment of HDAC2 to the promoter of the gene encoding the drug efflux pump ABCG2. Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored
expression and
repression and enhanced tumor sensitivity to doxorubicin. Our findings reveal transcriptional mechanisms regulating
that also regulate cancer stemness and chemoresistance and suggest that, by restoring
expression, aspirin might enhance chemotherapeutic efficacy in patients with stem-like tumors.</abstract><cop>United States</cop><pub>The American Association for the Advancement of Science</pub><pmid>33082288</pmid><doi>10.1126/scisignal.aay6077</doi><orcidid>https://orcid.org/0000-0003-4748-253X</orcidid><orcidid>https://orcid.org/0000-0002-9643-5396</orcidid><orcidid>https://orcid.org/0000-0002-9583-0693</orcidid><orcidid>https://orcid.org/0000-0001-5016-8918</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1945-0877 |
| ispartof | Science signaling, 2020-10, Vol.13 (654) |
| issn | 1945-0877 1937-9145 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2452979562 |
| source | American Association for the Advancement of Science |
| subjects | Anti-inflammatory agents Aspirin Breast cancer Chemoresistance Chemotherapy Colorectal carcinoma Cytotoxicity Doxorubicin Efflux Gene silencing HDAC2 protein Histone deacetylase Inflammation Invasiveness Nonsteroidal anti-inflammatory drugs Oct-4 protein Pluripotency Sensitivity enhancement Stem cell transplantation Stem cells Toxicity Tumor cells Tumors |
| title | SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T05%3A59%3A46IST&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=SMAR1%20repression%20by%20pluripotency%20factors%20and%20consequent%20chemoresistance%20in%20breast%20cancer%20stem-like%20cells%20is%20reversed%20by%20aspirin&rft.jtitle=Science%20signaling&rft.au=Bhattacharya,%20Apoorva&rft.date=2020-10-20&rft.volume=13&rft.issue=654&rft.issn=1945-0877&rft.eissn=1937-9145&rft_id=info:doi/10.1126/scisignal.aay6077&rft_dat=%3Cproquest_cross%3E2452979562%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=2453795933&rft_id=info:pmid/33082288&rfr_iscdi=true |