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Tamoxifen induces fatty liver disease in breast cancer through the MAPK8/FoxO pathway

Liuyun Gong1, Hanmin Tang1, Zhenzhen Luo1

  • 1Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, PR China.

Clinical and Translational Medicine
|June 9, 2020
PubMed
Abstract

Insights

Tamoxifen (TAM) can cause fatty liver disease in breast cancer patients. This study identified the MAPK8/FoxO signaling pathway as a key mechanism, offering insights for managing this side effect.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Metabolic complications of endocrine therapy for breast cancer are a clinical challenge.
  • Tamoxifen (TAM) is a common endocrine therapy linked to adverse effects like fatty liver disease (FLD).
  • Understanding the molecular basis of TAM-induced FLD is crucial for patient management.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying tamoxifen-induced fatty liver in breast cancer.
  • To identify direct protein targets of TAM and associated signaling pathways.
  • To validate the role of identified pathways in the development of TAM-induced FLD.

Main Methods:

  • Utilized DrugBank to identify direct protein targets (DPTs) of TAM.
  • Employed MalaCards to find significant genes in breast cancer and FLD.
  • Performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using STRING.
  • Validated findings through Western blot analysis.

Main Results:

  • Identified mitogen-activated protein kinase 8 (MAPK8) as a direct protein target of TAM.
  • Overlapping KEGG pathways between breast cancer and FLD included MAPK signaling, FoxO signaling, HIF-1 signaling, AGE-RAGE signaling, and PI3K-Akt signaling.
  • Confirmed that TAM may induce fatty liver in breast cancer via the MAPK8/FoxO signaling pathway.

Conclusions:

  • Bioinformatics approaches combined with experimental validation enhance understanding of cancer drug side effects.
  • The MAPK8/FoxO signaling pathway is implicated in tamoxifen-induced fatty liver.
  • This integrated methodology offers a new paradigm for studying drug-induced toxicities.
Keywords:
FoxO signaling pathwayMAPK8TAMbioinformatics analysisbreast cancerfatty liver

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