Disabled-1 is down-regulated in clinical breast cancer and regulates cell apoptosis through NF-κB/Bcl-2/caspase-9

J Cell Mol Med. 2019 Feb;23(2):1622-1627. doi: 10.1111/jcmm.14047. Epub 2018 Nov 28.

Abstract

Disabled-1 (Dab1) is best known as an adaptor protein regulating neuron migration and lamination during development. However, the exact function of Dab1 in breast cancer is unknown. In this study, we examined the expression of Dab1 in 38 breast cancer paraffin sections, as well as 60 paired frozen breast cancer and their adjacent tissues. Our results showed that Dab1 was reduced in breast cancer, and its compromised expression correlated with triple negative breast cancer phenotype, poor differentiation, as well as lymph node metastasis. Functional analysis in breast cancer cell lines demonstrated that Dab1 promoted cell apoptosis, which, at least partially, depended on its regulation of NF-κB/Bcl-2/caspase-9 pathway. Our study strongly suggests that Dab1 may be a potential tumour suppressor gene in breast cancer.

Keywords: NF-κB; breast cancer; cell apoptosis; clinical prognosis; disabled-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Caspase 9 / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MCF-7 Cells
  • Middle Aged
  • NF-kappa B / genetics
  • Nerve Tissue Proteins / genetics*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Transcription Factor RelA / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • bcl-2-Associated X Protein / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • BCL2 protein, human
  • DAB1 protein, human
  • NF-kappa B
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RELA protein, human
  • Transcription Factor RelA
  • bcl-2-Associated X Protein
  • CASP9 protein, human
  • Caspase 9