Downregulation of GEP100 Improved the Growth Inhibition Effect of Erlotinib Through Modulating Mesenchymal Epithelial Transition Process in Pancreatic Cancer

Xie, Chengrong; Sun, Shilong; Wei, Shumei; Xu, Xiaoming; Shao, Liming; Chen, Jiamin; Cai, Jianting

doi:10.1097/mpa.0000000000001076

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“…To this end, erlotinib is the first-line anti-tumor drug for the treatment of pancreatic cancer in the clinic [ 20 ]. Several human studies have verified the efficacy of erlotinib in improving the 5-year survival rate of patients with pancreatic cancer [ 21 , 22 ]. Molecular investigations report that several biological processes are modulated by erlotinib, including mTOR inhibition [ 23 ], epidermal growth factor receptor downregulation [ 24 ], and epidermal interstitial transformation (EMT) suppression [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

et al. 2018

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BackgroundMitochondrial 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.MethodsCell 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.ResultsThe 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.ConclusionsTogether, 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.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0665-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

et al. 2018

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Downregulation of GEP100 Improved the Growth Inhibition Effect of Erlotinib Through Modulating Mesenchymal Epithelial Transition Process in Pancreatic Cancer

Abstract: Our results suggested that GEP100 and E-cadherin have the predictive value for responsiveness to erlotinib in pancreatic cancer.

Cited by 1 publication

References 23 publications

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

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