The A20/TNFAIP3-CDC20-CASP1 Axis Promotes Inflammation-mediated Metastatic Disease in Triple-negative Breast Cancer

Christine Song, Ayse Tuba Kendi, Val J. Lowe, Seungbaek Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aim: The functions of the specific genes involved in the three types of breast cancer (BC) are unclear. Materials and Methods: A total of 53,805 genes were assessed from the RNA-sequencing database of BC cells and classified into those involved in hormonal positive (HR+) BC and triple-negative breast cancer (TNBC). Overall, distant metastasis-free, and relapse-free survival obtained from the Breast Cancer Gene-Expression Miner database containing 13,603 human breast cancer patient samples were assessed for gene associations using the RNA-sequencing database. To examine cell invasion and cytokine levels, inflammation-related genes were knocked down. The role of inflammation in cancer metastasis was confirmed using inflammatory inhibitors in a three-dimensional organoid ex vivo. Results: Genes affecting inflammation and cancer metastasis were highly expressed in TNBC, unlike HR+ BC. The A20/TNFAIP3-CDC20-CASP1 axis, which includes inflammation-related genes found in TNBC, was associated with poor patient prognosis, cancer metastasis, and cytokine levels. Inflammation inhibitors prevented the metastasis of aggressive TNBC. Conclusion: The A20/TNFAIP3-CDC20-CASP1 axis is closely related to the metastatic potential of TNBC, and inflammation inhibitors might be a novel target therapy for TNBC.

Original languageEnglish (US)
Pages (from-to)681-695
Number of pages15
JournalAnticancer research
Volume42
Issue number2
DOIs
StatePublished - Feb 2022

Keywords

  • A20/TNFAIP3
  • CASP1/Caspase-1
  • Cell division cycle 20 (Cdc20)
  • Inflammation
  • Inflammation inhibitors
  • Metastasis
  • Triple-negative breast cancer (TNBC)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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