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Orai1 is an Entotic Ca2+ Channel for Non-Apoptotic Cell Death, Entosis in Cancer Development

Ah Reum Lee1, Chan Young Park1

  • 1Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, 44919, Republic of Korea.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 24, 2023
PubMed

Insights

Intracellular calcium signaling regulates entosis, a cell death process in cancer, through the SEPTIN-Orai1-Ca2+/CaM-MLCK-actomyosin pathway. Orai1 calcium channels are key to this mechanism, offering potential therapeutic targets for tumors.

Area of Science:

  • Cell Biology
  • Cancer Biology
  • Molecular Mechanisms

Background:

  • Entosis is a non-apoptotic cell death pathway forming cell-in-cell structures in cancers.
  • Intracellular calcium (Ca2+) dynamics are crucial for various cellular functions, but their role in entosis remains unclear.

Purpose of the Study:

  • To elucidate the role of intracellular Ca2+ signaling and Ca2+ channels in the process of entosis.
  • To identify molecular players involved in Ca2+-mediated entosis.

Main Methods:

  • Investigated intracellular Ca2+ dynamics during entosis using live-cell imaging.
  • Utilized inhibitors and genetic manipulation of SEPTIN, Orai1, and MLCK.
  • Examined the effects of Ca2+ chelators on entosis.

Main Results:

  • Discovered that intracellular Ca2+ signaling regulates entosis via the SEPTIN-Orai1-Ca2+/CaM-MLCK-actomyosin axis.
  • Orai1 Ca2+ channels mediate spatiotemporal Ca2+ oscillations during cell engulfment.
  • SEPTIN filaments control Orai1 localization, activating MLCK and actomyosin contraction for cell internalization.

Conclusions:

  • Orai1 acts as a critical entotic Ca2+ channel, essential for Ca2+ signaling in entosis.
  • SEPTIN, Orai1, and MLCK are key components of the molecular mechanism driving entosis.
  • Targeting Orai1 presents a potential therapeutic strategy for entosis-associated cancers.
Keywords:
Orai1SEPTINcalcium signalingcell-in-cellentosis

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