Oxidative stress activates the TRPM2-Ca(2+)-CaMKII-ROS signaling loop to induce cell death in cancer cells

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Original languageEnglish
Pages (from-to)957-967
Journal / PublicationBiochimica et Biophysica Acta - Molecular Cell Research
Issue number6
Online published20 Dec 2016
Publication statusPublished - Jun 2017


High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca(2+)-permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca(2+) influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca(2+)-CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca(2+)-CaMKII-ROS signal loop to inhibit autophagy and induce cell death.

Research Area(s)

  • Autophagy, CaMKII, Ca2+, Oxidative stress, Reactive oxygen species, TRPM2

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Copyright © 2016 Elsevier B.V. All rights reserved.

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