Orai1 is an Entotic Ca2+ Channel for Non‐Apoptotic Cell Death, Entosis in Cancer Development
Abstract Entosis is a non‐apoptotic cell death process that forms characteristic cell‐in‐cell structures in cancers, killing invading cells. Intracellular Ca2+ dynamics are essential for cellular processes, including actomyosin contractility, migration, and autophagy. However, the significance of Ca...
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Wiley
2023-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202205913 |
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| author | Ah Reum Lee Chan Young Park |
| author_facet | Ah Reum Lee Chan Young Park |
| author_sort | Ah Reum Lee |
| collection | DOAJ |
| description | Abstract Entosis is a non‐apoptotic cell death process that forms characteristic cell‐in‐cell structures in cancers, killing invading cells. Intracellular Ca2+ dynamics are essential for cellular processes, including actomyosin contractility, migration, and autophagy. However, the significance of Ca2+ and Ca2+ channels participating in entosis is unclear. Here, it is shown that intracellular Ca2+ signaling regulates entosis via SEPTIN‐Orai1‐Ca2+/CaM‐MLCK‐actomyosin axis. Intracellular Ca2+ oscillations in entotic cells show spatiotemporal variations during engulfment, mediated by Orai1 Ca2+ channels in plasma membranes. SEPTIN controlled polarized distribution of Orai1 for local MLCK activation, resulting in MLC phosphorylation and actomyosin contraction, leads to internalization of invasive cells. Ca2+ chelators and SEPTIN, Orai1, and MLCK inhibitors suppress entosis. This study identifies potential targets for treating entosis‐associated tumors, showing that Orai1 is an entotic Ca2+ channel that provides essential Ca2+ signaling and sheds light on the molecular mechanism underlying entosis that involves SEPTIN filaments, Orai1, and MLCK. |
| format | Article |
| id | doaj-art-19a8f031f66b4829a1e4703e7a49ad8a |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-19a8f031f66b4829a1e4703e7a49ad8a2025-08-20T03:36:45ZengWileyAdvanced Science2198-38442023-05-011014n/an/a10.1002/advs.202205913Orai1 is an Entotic Ca2+ Channel for Non‐Apoptotic Cell Death, Entosis in Cancer DevelopmentAh Reum Lee0Chan Young Park1Department of Biological Sciences Ulsan National Institute of Science and Technology Ulsan 44919 Republic of KoreaDepartment of Biological Sciences Ulsan National Institute of Science and Technology Ulsan 44919 Republic of KoreaAbstract Entosis is a non‐apoptotic cell death process that forms characteristic cell‐in‐cell structures in cancers, killing invading cells. Intracellular Ca2+ dynamics are essential for cellular processes, including actomyosin contractility, migration, and autophagy. However, the significance of Ca2+ and Ca2+ channels participating in entosis is unclear. Here, it is shown that intracellular Ca2+ signaling regulates entosis via SEPTIN‐Orai1‐Ca2+/CaM‐MLCK‐actomyosin axis. Intracellular Ca2+ oscillations in entotic cells show spatiotemporal variations during engulfment, mediated by Orai1 Ca2+ channels in plasma membranes. SEPTIN controlled polarized distribution of Orai1 for local MLCK activation, resulting in MLC phosphorylation and actomyosin contraction, leads to internalization of invasive cells. Ca2+ chelators and SEPTIN, Orai1, and MLCK inhibitors suppress entosis. This study identifies potential targets for treating entosis‐associated tumors, showing that Orai1 is an entotic Ca2+ channel that provides essential Ca2+ signaling and sheds light on the molecular mechanism underlying entosis that involves SEPTIN filaments, Orai1, and MLCK.https://doi.org/10.1002/advs.202205913calcium signalingcell‐in‐cellentosisOrai1SEPTIN |
| spellingShingle | Ah Reum Lee Chan Young Park Orai1 is an Entotic Ca2+ Channel for Non‐Apoptotic Cell Death, Entosis in Cancer Development Advanced Science calcium signaling cell‐in‐cell entosis Orai1 SEPTIN |
| title | Orai1 is an Entotic Ca2+ Channel for Non‐Apoptotic Cell Death, Entosis in Cancer Development |
| title_full | Orai1 is an Entotic Ca2+ Channel for Non‐Apoptotic Cell Death, Entosis in Cancer Development |
| title_fullStr | Orai1 is an Entotic Ca2+ Channel for Non‐Apoptotic Cell Death, Entosis in Cancer Development |
| title_full_unstemmed | Orai1 is an Entotic Ca2+ Channel for Non‐Apoptotic Cell Death, Entosis in Cancer Development |
| title_short | Orai1 is an Entotic Ca2+ Channel for Non‐Apoptotic Cell Death, Entosis in Cancer Development |
| title_sort | orai1 is an entotic ca2 channel for non apoptotic cell death entosis in cancer development |
| topic | calcium signaling cell‐in‐cell entosis Orai1 SEPTIN |
| url | https://doi.org/10.1002/advs.202205913 |
| work_keys_str_mv | AT ahreumlee orai1isanentoticca2channelfornonapoptoticcelldeathentosisincancerdevelopment AT chanyoungpark orai1isanentoticca2channelfornonapoptoticcelldeathentosisincancerdevelopment |