Downregulation of TAB182 promotes cancer stem-like cell properties and therapeutic resistance in triple-negative breast cancer cells

Abstract

Table 182 participates in DNA damage repair and radio-/chemo-sensitivity regulation in various tumors, but its role in tumorigenesis and therapeutic resistance of breast cancer remains unclear. In the current paper, we observed that Triple-Negative Breast Cancer (TNBC), a highly aggressive type of breast cancer, exhibits a lower expression of TAB182. TAB182 knockdown stimulates cell proliferation, migration, and invasion in TNBC cells. Our study first constructed the RNA-seq data to explore the cellular functions of TAB182 at the genome level in TNBC cells. Transcriptome analysis and in vitro experiments identify that TAB182 downregulation drives the enhanced properties of cancer stem-like cells (CSCs) in TNBC cells. Furthermore, TAB182 deletion contributes to the resistance of cells to Olaparib or Cisplatin, which could be rescued by silencing GLI2, a downstream gene of cancer stemness-related signaling pathways. Our results reveal a novel function of TAB182 as a significant negative regulator of cancer stem-like properties and drug sensitivity in TNBC cells, suggesting TAB182 may be a tumor suppressor gene and associated with more therapeutic benefits for TNBC.