Protein C receptor maintains cancer stem cell properties via activating lipid synthesis in nasopharyngeal carcinoma

Metastasis and recurrence account for 95% of deaths from nasopharyngeal carcinoma (NPC). Cancer Stem Cells (CSCs) are regarded as one of the main reasons for tumor cell resistance to clinical therapy, and Cancer metastasis or recurrence, while little is known about CSCs in NPC. The present study uncovers a subpopulation of cells labeled as CD45^-EPCAM⁺PROCR⁺ in NPC biopsy samples that exhibit stem cell-like characteristics. A relatively low number of these cells initiate xenograft tumors in mice. Functional analysis reveals that protein C receptor (PROCR) not only serves as a stem cell marker in NPC, but also maintains tumor cells' stemness potential through regulating lipid metabolism and mitochondrial fission. Epistatic studies reveal that cAMP-protein kinase A stimulates Ca2⁺ release to manipulate lipid metabolism related genes' expression. Finally, in a cohort of 207 NPC samples, PROCR expression is correlated with tumor metastasis or recurrence, and predicts poor prognosis. These novel findings link PROCR labeled CSCs with lipid metabolism and mitochondrial plasticity, and provides new clinical target against metastatic or recurrent NPC.