HBXIP upregulates CD46, CD55 and CD59 through ERK1/2/NF-κB signaling to protect breast cancer cells from complement attack

FEBS Lett. 2012 Mar 23;586(6):766-71. doi: 10.1016/j.febslet.2012.01.039. Epub 2012 Jan 27.


Hepatitis B X-interacting protein (HBXIP) is able to enhance migration of breast cancer cells. However, the role of HBXIP in regulation of complement-dependent cytotoxicity (CDC) in breast cancer is not understood. Here, we report that HBXIP contributes to protecting breast cancer cells from CDC by upregulating membrane-bound complement regulatory protein (mCRPs), including CD46, CD55 and CD59. We found that HBXIP upregulated mCRPs through activating p-ERK1/2/NF-κB. Interestingly, the knockdown of CD59 was able to block the HBXIP-enhanced breast tumor growth in animal. Thus, we conclude that HBXIP upregulates CD46, CD55 and CD59 through p-ERK1/2/NF-κB signaling to protect breast cancer from CDC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology*
  • Animals
  • Breast Neoplasms / immunology*
  • CD55 Antigens / immunology*
  • CD59 Antigens / immunology*
  • Complement Activation / immunology
  • Complement System Proteins / immunology*
  • Female
  • Humans
  • MAP Kinase Signaling System / immunology*
  • Membrane Cofactor Protein / immunology*
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-kappa B / immunology*
  • Trans-Activators / immunology
  • Tumor Cells, Cultured
  • Viral Regulatory and Accessory Proteins


  • Adaptor Proteins, Signal Transducing
  • CD55 Antigens
  • CD59 Antigens
  • LAMTOR5 protein, human
  • Membrane Cofactor Protein
  • NF-kappa B
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • Complement System Proteins
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3