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Updated: Oct 5, 2025

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
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Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples

Published on: October 2, 2020

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FOXM1 mediates GDF-15 dependent stemness and intrinsic drug resistance in breast cancer

Anupama Modi1, Purvi Purohit2, Dipayan Roy1

  • 1Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, India.

Molecular Biology Reports
|January 23, 2022
PubMed
Abstract

Insights

Growth Differentiation Factor-15 (GDF-15) promotes stemness and chemoresistance in breast cancer (BC). This study found GDF-15 significantly increased in BC patients, correlating with stemness and drug resistance markers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Stemness contributes to breast cancer (BC) heterogeneity and chemoresistance.
  • Growth Differentiation Factor-15 (GDF-15) is implicated in inducing drug resistance and stemness in BC cells.

Purpose of the Study:

  • To evaluate the expressions and interactions of GDF-15, FOXM1, stemness markers (OCT4, SOX2), and drug resistance marker (ABCC5) in BC.
  • To elucidate the signaling pathway involved in GDF-15-mediated stemness and drug resistance.

Main Methods:

  • Serum GDF-15 levels were measured in 40 BC patients and 40 controls.
  • Gene expressions (GDF-15, OCT4, SOX2, FOXM1, ABCC5) and phosphorylated AKT (p-AKT) were analyzed in BC tissues and cell lines (MCF-7, MDA-MB-231) using RT-PCR and Western blot.
  • GDF-15 knockdown and recombinant GDF-15 treatment were performed to analyze the signaling pathway. In silico analyses were conducted using UALCAN.

Main Results:

  • Serum GDF-15 was significantly elevated in BC patients compared to controls.
  • Expressions of GDF-15, OCT4, SOX2, FOXM1, and p-AKT were significantly higher in BC tissues and MDA-MB-231 cells compared to controls and MCF-7 cells, respectively.
  • GDF-15 expression positively correlated with ABCC5, OCT4, SOX2, and FOXM1. GDF-15 knockdown reduced p-AKT, FOXM1, OCT4, SOX2, and ABCC5 expression, which was reversed by recombinant GDF-15 treatment.

Conclusions:

  • GDF-15 significantly promotes stemness and intrinsic drug resistance in breast cancer.
  • The p-AKT/FOXM1 signaling axis is likely involved in mediating GDF-15's effects on stemness and drug resistance in BC.
Keywords:
Breast cancerDrug resistanceFOXM1GDF-15StemnessTriple negative breast cancer

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