To survive, cancer cells require an adequate supply of nutrients to meet their biosynthetic and bioenergetic needs and to maintain appropriate redox balance. One of the most abundant and important nutrients supporting cancer cell survival is glutamine. The cystine-glutamate antiporter protein xCT (SLC7A11), is the light and substrate-specific subunit of the heterodimeric amino-acid transport system xc- It is characterized by 12 multi-pass transmembrane and 6 extracellular domains (named ECD1-6) with intracellular N- and C-terminals. xCT mediates the exportation of the intracellular glutamate and the importation of extracellular cystine. The cystine is converted to cysteine required for glutathione (GSH) synthesis. GSH is important for the cell protection against oxidative stress and chemical insults.
xCT expression is highly restricted to a few normal cell types (neurons and a subset of macrophages), and xCT knockout mice show no developmental or growth defects. On the contrary, elevated levels of xCT protein are observed in a high percentage of invasive mammary ductal tumors including TNBC and correlates with poor overall survival. Indeed increased xCT expression has been correlated with breast cancer invasiveness and epithelial to mesenchymal transition. Furthermore, xCT over-expressing cells have been found enriched in tumorspheres, highlighting a role of xCT in promoting the cancer stem cell phenotype.
Thus, xCT possesses all the features of an ideal target for antibody-based therapies against undifferentiated and more differentiated cancer cells. Our analysis performed on several neoplastic tissues and data obtained by other investigators, have identified xCT as a distinctive marker for a wide range of cancers including metastatic, colonrectal, lung , pancreatic, hepatocellular cancers and glioblastoma.