Survival of detached cancer cells is regulated by movement of intracellular Na+,K+-ATPase

Summary Beginning of metastasis, cancer cells detach from the primary tumor and they can survive even under loss of anchorage, however, the detachment-elicited mechanisms have remained unknown. Here we found that Na+,K+-ATPase α3-isoform (α3NaK) in human cancer cells is dynamically translocated from intracellular vesicles to the plasma membrane when the attached cells are detached and that this mechanism contributes to the survival of the detached (floating) cancer cells. α3NaK was detected in the plasma membrane of floating cancer cells in peritoneal fluids of patients, while it was in the cytoplasm of the cells in primary tumor tissues. Upon cancer cell detachment, we also found the FAK-dependent Ca2+ response which induces the α3NaK translocation via NAADP pathway. Activation of AMPK was associated with the translocated α3NaK in the plasma membrane. Collectively, our study identifies a unique mechanism for survival of detached cancer cells, opening up new opportunities for development of cancer medicines.