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

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 in...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099779/
https://www.ncbi.nlm.nih.gov/pubmed/33997694
http://dx.doi.org/10.1016/j.isci.2021.102412
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author 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
author_facet 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
author_sort Fujii, Takuto
collection PubMed
description 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 Ca(2+) 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.
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spelling pubmed-80997792021-05-13 Survival of detached cancer cells is regulated by movement of intracellular Na(+),K(+)-ATPase 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 iScience Article 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 Ca(2+) 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. Elsevier 2021-04-15 /pmc/articles/PMC8099779/ /pubmed/33997694 http://dx.doi.org/10.1016/j.isci.2021.102412 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
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
Survival of detached cancer cells is regulated by movement of intracellular Na(+),K(+)-ATPase
title Survival of detached cancer cells is regulated by movement of intracellular Na(+),K(+)-ATPase
title_full Survival of detached cancer cells is regulated by movement of intracellular Na(+),K(+)-ATPase
title_fullStr Survival of detached cancer cells is regulated by movement of intracellular Na(+),K(+)-ATPase
title_full_unstemmed Survival of detached cancer cells is regulated by movement of intracellular Na(+),K(+)-ATPase
title_short Survival of detached cancer cells is regulated by movement of intracellular Na(+),K(+)-ATPase
title_sort survival of detached cancer cells is regulated by movement of intracellular na(+),k(+)-atpase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099779/
https://www.ncbi.nlm.nih.gov/pubmed/33997694
http://dx.doi.org/10.1016/j.isci.2021.102412
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