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USP18 reduces paclitaxol sensitivity of triple-negative breast cancer via autophagy

Xiangwei Ge1, Deyu Zhang2, Songze Song3

  • 1Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, 100850, China; Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100071, China.

Biochemical and Biophysical Research Communications
|February 18, 2022
PubMed

Insights

USP18 promotes paclitaxol resistance in triple-negative breast cancer (TNBC) by inducing autophagy. Inhibiting USP18 or autophagy can restore sensitivity to paclitaxol, offering a potential therapeutic strategy for TNBC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Paclitaxol is a key treatment for triple-negative breast cancer (TNBC).
  • Mechanisms of paclitaxol resistance in TNBC are not fully understood.
  • Identifying resistance mechanisms is crucial for improving TNBC therapy.

Purpose of the Study:

  • To investigate the role of differentially expressed genes (DEGs) in paclitaxol resistance in TNBC.
  • To identify potential therapeutic targets for overcoming paclitaxol resistance.
  • To elucidate the molecular mechanisms by which USP18 influences paclitaxol sensitivity.

Main Methods:

  • Bioinformatic analysis of gene expression in TNBC and paclitaxol-resistant TNBC cells.
  • In vitro and in vivo experiments assessing the effects of USP18 modulation on paclitaxol sensitivity.
  • Investigation of USP18's role in regulating autophagy.
  • Utilizing autophagy inhibitors to assess their impact on USP18-mediated resistance.

Main Results:

  • USP18 mRNA expression was significantly elevated in paclitaxol-resistant TNBC cells.
  • USP18 overexpression decreased paclitaxol-induced apoptosis and cell cycle arrest.
  • USP18 knockdown enhanced anticancer activity of paclitaxol in vitro and in vivo.
  • USP18 was found to induce autophagy, a known mechanism of chemotherapy resistance.
  • Autophagy inhibition reversed the paclitaxol resistance phenotype induced by USP18.

Conclusions:

  • USP18 plays a significant role in mediating paclitaxol resistance in TNBC.
  • USP18 promotes resistance by inducing autophagy.
  • USP18 represents a potential therapeutic target for overcoming paclitaxol resistance in TNBC patients.
Keywords:
AutophagyPaclitaxol resistanceTriple negative breast cancerUbiquitin specific peptidase 18

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