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

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.

• Authors: Christine Song, Ayse Tuba Kendi, Val J Lowe, Seungbaek Lee
• Journal: Anticancer research (Anticancer Res) Vol. 42 Issue 2 Pg. 681-695 (Feb 2022) ISSN: 1791-7530 [Electronic] Greece
• PMID: 35093867 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Cdc20 Proteins
• Cytokines
• Inflammation Mediators
• CDC20 protein, human
• TNFAIP3 protein, human
• Tumor Necrosis Factor alpha-Induced Protein 3
• Caspase 1

Topics

• Breast Neoplasms (genetics, metabolism, pathology)
• Caspase 1 (genetics)
• Cdc20 Proteins (genetics)
• Cell Line, Tumor
• Cytokines (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Inflammation
• Inflammation Mediators (metabolism)
• Neoplasm Metastasis
• Prognosis
• Triple Negative Breast Neoplasms (genetics, metabolism, pathology)
• Tumor Necrosis Factor alpha-Induced Protein 3 (genetics)