iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca 2+ homeostasis and control tumor growth and drug resistance

Abstract

Significance Accumulating preclinical and clinical evidence has supported a central role for alterations in Ca 2+ homeostasis in the development of cancer. TMCO1 protein is an identified Ca 2+ -channel protein, while its roles in cancer remain obscure. Here, we found that TMCO1 is increased in colon cancer tissues. In addition, it is a substrate of E3 ligase Gp78. Enhanced oncogene iASPP stabilizes TMCO1 by competitively binding with Gp78. Inhibition of iASPP-TMCO1 sensitizes cancer cells’ response to Ca 2+ -induced apoptosis. This study has improved our fundamental understanding of the Ca 2+ homeostasis in cancer cells. iASPP-TMCO1 axis may present a promising therapeutic target that can combine the conventional drugs to reinforce Ca 2+ -dependent apoptosis.