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Cancer Cell International
Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Primary research

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

Authors: Jun Wan, Jie Cui, Lei Wang, Kunpeng Wu, Xiaoping Hong, Yulin Zou, Shuang Zhao, Hong Ke

Published in: Cancer Cell International | Issue 1/2018

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Abstract

Background

Mitochondrial fragmentation drastically regulates the viability of pancreatic cancer through a poorly understood mechanism. The present study used erlotinib to activate mitochondrial fragmentation and then investigated the downstream events that occurred in response to mitochondrial fragmentation.

Methods

Cell viability and apoptosis were determined via MTT assay, TUNEL staining and ELISA. Mitochondrial fragmentation was measured via an immunofluorescence assay and qPCR. siRNA transfection and pathway blockers were used to perform the loss-of-function assays.

Results

The results of our study demonstrated that erlotinib treatment mediated cell apoptosis in the PANC-1 pancreatic cancer cell line via evoking mitochondrial fragmentation. Mechanistically, erlotinib application increased mitochondrial fission and reduced mitochondrial fusion, triggering mitochondrial fragmentation. Subsequently, mitochondrial fragmentation caused the overproduction of mitochondrial ROS (mROS). Interestingly, excessive mROS induced cardiolipin oxidation and mPTP opening, finally facilitating HtrA2/Omi liberation from the mitochondria into the cytoplasm, where HtrA2/Omi activated caspase-9-dependent cell apoptosis. Notably, neutralization of mROS or knockdown of HtrA2/Omi attenuated erlotinib-mediated mitochondrial fragmentation and favored cancer cell survival.

Conclusions

Together, our results identified the mROS-HtrA2/Omi axis as a novel signaling pathway that is activated by mitochondrial fragmentation and that promotes PANC-1 pancreatic cancer cell mitochondrial apoptosis in the presence of erlotinib.
Appendix
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Metadata
Title
RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways
Authors
Jun Wan
Jie Cui
Lei Wang
Kunpeng Wu
Xiaoping Hong
Yulin Zou
Shuang Zhao
Hong Ke
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-018-0665-1

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