| abstract |
High mitochondrial ATP is a metabolic trait that confers hyper-proliferation, stemness, anchorage-independence, anti-oxidant capacity and multi-drug resistance in cancer cells. Under the present approach, intracellular ATP levels may be used as a metabolic biomarker to identify, separate, and purify an aggressive and hyper-proliferative cancer stem cell ("CSC") phenotype. Further, ATP may be combined with other CSC markers, e.g., CD44 or ALDH-activity, to beneficially fractionate the CSC population into sub-populations. For example, ATP-high/ CD44-high CSC sub-populations showed twice the level of anchorage-independent growth compared to ATP-low/CD44-high CSC sub-populations. Also disclosed are complementary bioinformatic data that implicate mitochondrial ATP synthesis in stemness, metastasis, and the detection of circulating tumor cells ("CTCs"), and a five-member, ATP-related metastasis gene-signature (ABCA2, ATP5F1C, COX20, NDUFA2 and UQCRB). The gene signature of the present approach may be used to identify CSCs having a dramatic increase in cell migration and invasion in vitro capacity, as well as spontaneous metastasis in vivo. The present approach also provides a cellular platform for systematically targeting stemness, multi-drug resistance, and metastasis in cancer cells. |