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

• Published in: iScience 2021-05, Vol.24 (5), p.102412-102412, Article 102412
• Main Authors: Fujii, Takuto, Shimizu, Takahiro, Katoh, Mizuki, Nagamori, Shushi, Koizumi, Keiichi, Fukuoka, Junya, Tabuchi, Yoshiaki, Sawaguchi, Akira, Okumura, Tomoyuki, Shibuya, Kazuto, Fujii, Tsutomu, Takeshima, Hiroshi, Sakai, Hideki
• Format: Article
• Language: English
• Subjects: Cancer; Cell Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.102412

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. On cancer cell detachment, we also found the focal-adhesion-kinase-dependent Ca2+ response that induces the α3NaK translocation via nicotinic acid adenine dinucleotide phosphate pathway. Activation of AMP-activated protein kinase 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. [Display omitted] •Na+,K+-ATPase α3-isoform (α3NaK) is localized in cytoplasm of attached cancer cells•Intracellular α3NaK is moved to plasma membrane (PM) upon the cell detachment•FAK and NAADP-dependent Ca2+ response is involved in the translocation of α3NaK•Activation of AMPK associated with the PM-α3NaK contributes to the cell survival Cell Biology; Cancer