Z Gastroenterol 2022; 60(01): e39-e40
DOI: 10.1055/s-0041-1740780
Abstracts | GASL

Cold shock protein YB-1 upregulates MDR1 transcription and thus contributes to cholangiocarcinoma chemoresistance to cisplatin

Authors

  • Tao Lin

    1   Heidelberg University

  • Heng Liu

    1   Heidelberg University

  • Jon Lindquist

    1   Heidelberg University

  • Peter Mertens

    1   Heidelberg University

  • Matthias Ebert

    1   Heidelberg University

  • Steven Dooley

    1   Heidelberg University

  • Jun Li

    1   Heidelberg University

  • Stefan Munker

    1   Heidelberg University

  • Honglei Weng

    1   Heidelberg University
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    Background & Aim Cholangiocarcinoma is a liver cancer with high mortality. Chemotherapy with cisplatin or gemcitabine is a main approach to treat cholangiocarcinoma patients at advanced stage. However, efficiency of these drugs is poor due to chemoresistance. To date, detailed mechanisms underlying chemoresistance in cholangiocarcinoma remain largely unknown. In this study, we demonstrate a crucial role for the cold shock protein Y-box binding protein-1 (YB-1) in cholangiocarcinoma chemoresistance to cisplatin.

    Methods Expression of YB-1 was examined by immunohistochemistry in 28 cholangiocarcinoma patients receiving surgery. Among them, 10 patients received chemotherapy following operation. The function and relevant mechanisms of YB-1 in cholangiocarcinoma were investigated in vitro.

    Results YB-1 expression in cancer cells, in particular in nuclei, was closely associated with survival of patients. From 10 patients receiving chemotherapy, 2 patients without YB-1 expression, but only 3 out of 8 patients with YB-1 expression survived a 5-year follow-up. In vitro, immunofluorescence staining showed that cisplatin administration resulted in YB-1 nuclear translocation. ChIP assays further demonstrated YB-1 binding to the multidrug resistance gene MDR1 promoter prior to expression induction. Impressively, administration of cisplatin significantly increased YB-1 binding to the MDR1 promoter. Functionally, knockdown of YB-1 by RNAi inhibited cancer cell proliferation and increased cisplatin-dependent apoptosis.

    Conclusions YB-1 nuclear expression plays a crucial role in cholangiocarcinoma chemoresistance to cisplatin treatment through upregulating MDR1 expression. YB-1 expression in cancer cells might be a useful biomarker to determine chemotherapy in cholangiocarcinoma. Disruption of YB-1 is a potential approach to treat cholangiocarcinoma in clinical


     

    Publikationsverlauf

    Artikel online veröffentlicht:
    26. Januar 2022

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