Creatine kinase B promotes non–small cell lung cancer survival and metastasis

Creatine kinase (CK) catalyzes the reversible transfer of a phosphoryl group from ATP to creatine. There are four distinct CK genes (CKM [muscle-type CK], CKB [brain-type CK], CKMT1 [ubiquitous-type CK], and CKMT2 [sarcomeric-type CK]) with cell-type selective expression and subcellular localization. In cancer, uncontrolled cell proliferation drives aggressive migration and invasion into nearby tissues and distant organs. While creatine metabolism is known to support cancer cell survival, the specific roles of individual CK isoenzymes remain unclear. Here, we demonstrate that CKB is essential for CK enzymatic activity in several cancer cell lines, including non-small cell lung cancer (H1299), osteosarcoma (143B), and ovarian adenocarcinoma (OVCAR8). Moreover, we demonstrate that CKB promotes metastasis of H1299 cells to the lung and liver in vivo, a process associated with enhanced anoikis resistance.