SMAGP regulates doxorubicin sensitivity in triple-negative breast cancer cells via modulating mitochondrial respiration

Doxorubicin-based chemotherapy remains as a major therapeutic approach for patients with triple-negative breast cancer (TNBC). However, insensitivity or resistance to doxorubicin treatment limits the therapeutic efficacy. Mitochondrial respiration plays a critical role in regulating the sensitivity of cancer cells to chemotherapy drugs. Here, we found that small trans-membrane and glycosylated protein (SMAGP) is upregulated in TNBC cells in comparison to normal breast and other subtypes of breast cancer cells. High SMAGP expression is associated with poorer overall survival of TNBC patients. Importantly, loss of SMAGP enhanced the sensitivity of TNBC cells to doxorubicin treatment. Mechanistically, we detected a functional pool of SMAGP in the mitochondria of TNBC cells controlling doxorubicin sensitivity via regulating mitochondrial respiration. Thus, our data suggest that SMAGP acts as a novel regulator of doxorubicin sensitivity in TNBC, identifying SMAGP as a promising therapeutic target for improving the efficacy of doxorubicin-based chemotherapy in TNBC patients.