Elevated PAF1-RAD52 axis confers chemoresistance to human cancers

Sanchita Rauth, Koelina Ganguly, Pranita Atri, Seema Parte, Rama Krishna Nimmakayala, Venkatesh Varadharaj, Palanisamy Nallasamy, Raghupathy Vengoji, Ayoola O. Ogunleye, Imayavaramban Lakshmanan, Ramakanth Chirravuri, Mika Bessho, Jesse L. Cox, Jason M. Foster, Geoffrey A. Talmon, Tadayoshi Bessho, Apar Kishor Ganti, Surinder K. Batra, Moorthy P. Ponnusamy

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number112043
JournalCell Reports
Volume42
Issue number2
DOIs
StatePublished - Feb 28 2023

Keywords

  • CP: Cancer
  • DNA repair
  • PAF1
  • RAD52
  • chemoresistance
  • lung cancer
  • ovarian cancer
  • pancreatic cancer

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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