MAGEA1 interacts with FBXW7 and regulates ubiquitin ligase-mediated turnover of NICD1 in breast and ovarian cancer cells

Oncogene. 2017 Aug 31;36(35):5023-5034. doi: 10.1038/onc.2017.131. Epub 2017 May 1.


Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cancers, its functional role and signaling mechanisms are largely unknown. In this study, we examined the functional involvement and signaling mechanisms of MAGEA1 in breast and ovarian cancer cells. Inhibitory effects of MAGEA1 on cell proliferation and migration were observed using both gain-of- (MAGEA1 overexpression) and loss-of- (siRNA interference) function approaches in breast (MCF-7 and MDA-MB-231) and ovarian (SKOV3 and SKOV3ip) cancer cell lines. We revealed a novel interaction between MAGEA1 and the intracellular segment of NOTCH1 receptor (NICD1). MAGEA1 reduced NICD1's stability by promoting the ubiquitin modification of NICD1. MAGEA1 also interacted with FBXW7, subunit of E3 ubiquitin protein ligase complex SCF, and the latter was functionally involved in NICD1 ubiquitination and degradation. In addition, siRNA interference of FBXW7 reversed the inhibitory effect of MAGEA1 on migration and proliferation of MCF-7 and MDA-MB-231 cells. These newly discovered MAGEA1-NICD1 and MAGEA1-FBXW7 interactions have potential clinical implications in breast and ovarian cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism*
  • F-Box-WD Repeat-Containing Protein 7
  • Female
  • Humans
  • MCF-7 Cells
  • Melanoma-Specific Antigens / genetics
  • Melanoma-Specific Antigens / metabolism*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Signal Transduction
  • Transfection
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination


  • Cell Cycle Proteins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Receptor, Notch1
  • Ubiquitin-Protein Ligases