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.