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

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.