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Elevated PAF1-RAD52 axis confers chemoresistance to human cancers
Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human can...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374878/ https://www.ncbi.nlm.nih.gov/pubmed/36709426 http://dx.doi.org/10.1016/j.celrep.2023.112043 |
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author | Rauth, Sanchita Ganguly, Koelina Atri, Pranita Parte, Seema Nimmakayala, Rama Krishna Varadharaj, Venkatesh Nallasamy, Palanisamy Vengoji, Raghupathy Ogunleye, Ayoola O. Lakshmanan, Imayavaramban Chirravuri, Ramakanth Bessho, Mika Cox, Jesse L. Foster, Jason M. Talmon, Geoffrey A. Bessho, Tadayoshi Kishor Ganti, Apar Batra, Surinder K. Ponnusamy, Moorthy P. |
author_facet | Rauth, Sanchita Ganguly, Koelina Atri, Pranita Parte, Seema Nimmakayala, Rama Krishna Varadharaj, Venkatesh Nallasamy, Palanisamy Vengoji, Raghupathy Ogunleye, Ayoola O. Lakshmanan, Imayavaramban Chirravuri, Ramakanth Bessho, Mika Cox, Jesse L. Foster, Jason M. Talmon, Geoffrey A. Bessho, Tadayoshi Kishor Ganti, Apar Batra, Surinder K. Ponnusamy, Moorthy P. |
author_sort | Rauth, Sanchita |
collection | PubMed |
description | Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression of PAF1 contributes to chemotherapy resistance and worse clinical outcome for lethal cancers. |
format | Online Article Text |
id | pubmed-10374878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-103748782023-10-23 Elevated PAF1-RAD52 axis confers chemoresistance to human cancers Rauth, Sanchita Ganguly, Koelina Atri, Pranita Parte, Seema Nimmakayala, Rama Krishna Varadharaj, Venkatesh Nallasamy, Palanisamy Vengoji, Raghupathy Ogunleye, Ayoola O. Lakshmanan, Imayavaramban Chirravuri, Ramakanth Bessho, Mika Cox, Jesse L. Foster, Jason M. Talmon, Geoffrey A. Bessho, Tadayoshi Kishor Ganti, Apar Batra, Surinder K. Ponnusamy, Moorthy P. Cell Rep Article Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression of PAF1 contributes to chemotherapy resistance and worse clinical outcome for lethal cancers. 2023-02-28 2023-01-28 /pmc/articles/PMC10374878/ /pubmed/36709426 http://dx.doi.org/10.1016/j.celrep.2023.112043 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Rauth, Sanchita Ganguly, Koelina Atri, Pranita Parte, Seema Nimmakayala, Rama Krishna Varadharaj, Venkatesh Nallasamy, Palanisamy Vengoji, Raghupathy Ogunleye, Ayoola O. Lakshmanan, Imayavaramban Chirravuri, Ramakanth Bessho, Mika Cox, Jesse L. Foster, Jason M. Talmon, Geoffrey A. Bessho, Tadayoshi Kishor Ganti, Apar Batra, Surinder K. Ponnusamy, Moorthy P. Elevated PAF1-RAD52 axis confers chemoresistance to human cancers |
title | Elevated PAF1-RAD52 axis confers chemoresistance to human cancers |
title_full | Elevated PAF1-RAD52 axis confers chemoresistance to human cancers |
title_fullStr | Elevated PAF1-RAD52 axis confers chemoresistance to human cancers |
title_full_unstemmed | Elevated PAF1-RAD52 axis confers chemoresistance to human cancers |
title_short | Elevated PAF1-RAD52 axis confers chemoresistance to human cancers |
title_sort | elevated paf1-rad52 axis confers chemoresistance to human cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374878/ https://www.ncbi.nlm.nih.gov/pubmed/36709426 http://dx.doi.org/10.1016/j.celrep.2023.112043 |
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