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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; Ganti, Apar Kishor; Batra, Surinder K; Ponnusamy, Moorthy P.
Afiliação
  • Rauth S; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Ganguly K; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Atri P; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Parte S; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Nimmakayala RK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Varadharaj V; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Nallasamy P; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Vengoji R; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Ogunleye AO; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Lakshmanan I; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Chirravuri R; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Bessho M; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Cox JL; Department of Pathology and Microbiology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Foster JM; Department of Surgery, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Talmon GA; Department of Pathology and Microbiology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Bessho T; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
  • Ganti AK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA; Division of Oncology-Hematology, Department of Internal Medicine, VA Nebraska Western Iowa Health Care System, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buff
  • Batra SK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA. Electronic address: sb
  • Ponnusamy MP; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA. Electronic address: mp
Cell Rep ; 42(2): 112043, 2023 02 28.
Article em En | MEDLINE | ID: mdl-36709426
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Resistencia a Medicamentos Antineoplásicos / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Resistencia a Medicamentos Antineoplásicos / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article