TRPS1 Confers Multidrug Resistance of Breast Cancer Cells by Regulating BCRP Expression

Jing Hu1, Hui Zhang1, Long Liu1

  • 1Department of Pathology, Qilu Hospital of Shandong University, Jinan, China.

Frontiers in Oncology
|July 23, 2020
PubMed

Insights

High TRPS1 expression in breast cancer (BCa) drives multidrug resistance (MDR) by increasing BCRP, a key transporter. Inhibiting TRPS1 may restore chemosensitivity in BCa treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Multidrug resistance (MDR) significantly hinders effective breast cancer (BCa) treatment.
  • Understanding the molecular mechanisms of chemoresistance is crucial for therapeutic advancement.
  • Previous studies suggest a link between TRPS1 and breast cancer progression.

Purpose of the Study:

  • To investigate the specific role of TRPS1 in the development of chemoresistance in breast cancer.
  • To elucidate the molecular pathway through which TRPS1 influences drug resistance.
  • To identify TRPS1 as a potential therapeutic target for overcoming MDR in BCa.

Main Methods:

  • Bioinformatic analysis of publicly available breast cancer datasets.
  • In vitro experiments involving manipulation of TRPS1 expression in BCa cells.
  • Assessment of BCRP expression and function.
  • Immunohistochemical analysis of TRPS1 and BCRP correlation in patient samples.
  • MTT assays to evaluate chemosensitivity.

Main Results:

  • TRPS1 overexpression was correlated with chemoresistance in breast cancer data.
  • TRPS1 directly regulates the expression of BCRP, a drug efflux transporter.
  • Upregulation of TRPS1 increased BCRP levels, while TRPS1 inhibition decreased BCRP.
  • A significant correlation between TRPS1 and BCRP was observed in 180 BCa patient samples.
  • Modulating TRPS1 expression altered the chemosensitivity of breast cancer cells.

Conclusions:

  • High TRPS1 expression confers multidrug resistance in breast cancer.
  • This MDR is mediated through the regulation of BCRP expression and function.
  • TRPS1 represents a novel mechanism contributing to BCa chemoresistance.
  • Targeting TRPS1 could offer a new strategy to overcome chemoresistance in breast cancer treatment.

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