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  11. Pfdn4 As A Prognostic Marker Was Associated With Chemotherapy Resistance Through Crebp1/aurka Pathway In Triple-negative Breast Cancer

PFDN4 as a Prognostic Marker Was Associated with Chemotherapy Resistance through CREBP1/AURKA Pathway in Triple-Negative Breast Cancer

Shih-Ho Wang1, Cheng-Hsi Yeh1, Chia-Wei Wu2

  • 1Division of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.

International Journal of Molecular Sciences
|April 13, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Prefolded proteins 4 (PFDN4) are highly expressed in breast cancer, correlating with poor prognosis. Targeting PFDN4 inhibits cancer growth and may overcome chemotherapy resistance, particularly in triple-negative breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Breast cancer incidence is rising, with chemotherapy resistance a significant clinical challenge.
  • Prefolded proteins 4 (PFDN4) are crucial molecular chaperones involved in protein folding and stability.
  • The role of PFDN4 in breast cancer chemoresistance is not well understood.

Purpose of the Study:

  • To investigate the role of PFDN4 in the development of chemotherapy resistance in breast cancer.
  • To determine the association of PFDN4 expression with breast cancer patient survival and clinicopathological features.

Main Methods:

  • Analysis of PFDN4 expression in breast cancer tissues using TCGA database.
  • CRISPR-Cas9 gene editing to knock out PFDN4 in breast cancer cell lines.
  • Investigating the PFDN4/CREBP1/AURKA pathway in triple-negative breast cancer cells.
Keywords:
PFDN4chemotherapy resistancetriple-negative breast cancer

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Main Results:

  • PFDN4 is significantly overexpressed in breast cancer tissues compared to normal tissues.
  • High PFDN4 expression correlates with advanced stage, nodal involvement, and poorer disease-specific survival.
  • CRISPR knockout of PFDN4 inhibited 89% of breast cancer cell lines, with a stronger effect in triple-negative subtypes.
  • High PFDN4 expression is linked to poor survival and resistance to doxorubicin and paclitaxel via the CREBP1/AURKA pathway in triple-negative breast cancer.

Conclusions:

  • PFDN4 is a potential biomarker for poor prognosis in breast cancer.
  • Targeting PFDN4 may represent a novel therapeutic strategy to overcome chemotherapy resistance, especially in triple-negative breast cancer.