Suzuki-Karasaki 2015 Abstract MiP2015

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L-type calcium channels prevent mitochondrial network disruption in human cancer cells.

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Suzuki-Karasaki Y (2015)

Event: MiP2015

Recently, we reported that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces an excessive fragmentation and clustering of the mitochondria in various human cancer cells, including malignant melanoma, but not in non-transformed cells [1]. TRAIL resistant tumor cells are resistant to this pro-apoptotic mitochondrial structure disruption, and dynamin-related protein 1 (Drp1)-dependent mitochondrial fission contributes to this resistance. Here we identify L-type Ca2+ channels (LTCCs) as an important regulator of TRAIL resistance and mitochondrial structure remodeling. We found that melanoma cells expressing high levels of Cav1.2 and Cav1.3 were more resistant than cells expressing low levels of Cav1.2 or Cav1.3 to spontaneous and TRAIL-induced cell death. In addition, the mitochondria within the latter, but not the former, displayed considerable structural abnormalities, characterized by excessive fragmentation and clustering. Downregulation of either Cav1.2 or Cav1.3 by RNA interference increased mitochondrial structural abnormalities and sensitized to spontaneous cell death. On the other hand, downregulation of Cav1.2, but not Cav1.3, sensitized to TRAIL-induced apoptosis via the intrinsic apoptotic pathway. Moreover, mitochondrial Ca2+ uptake via LTCCs regulated the Drp1-dependent pro-survival mitochondrial remodeling. Altogether, these findings provide the first evidence that LTCCs play an important role in survival, drug resistance, and mitochondrial remodeling in cancer cells.


Labels: MiParea: Comparative MiP;environmental MiP, mt-Medicine  Pathology: Cancer  Stress:Cell death  Organism: Human 




Event: A2, Oral  MiP2015 

Affiliations

1-Div Physiol, Dept Biomed Sci, Nihon Univ Sch Med; 2-Innovative Ther Res Group, Nihon Univ Res Inst Med Sci, Tokyo, Japan. - suzuki.yoshihiro@nihon-u.ac.jp

References and acknowledgements

  1. Suzuki-Karasaki Y, Fujiwara K, Saito K, Suzuki-Karasaki M, Ochiai T, Soma M (2015) Distinct effects of TRAIL on the mitochondrial network in human cancer cells and normal cells: role of plasma membrane depolarization. Oncotarget Advance Online Publications 6:21572-88.