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SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer

BACKGROUND: Autophagy is a cell degradation pathway that eliminates damaged or unwanted proteins and organelles. Autophagy protects cells from chemotherapeutic agents by scavenging damaged mitochondria. METHODS: Plasmid transfection and shRNA were used to regulate SHP-2 expression. Annexin V/PI stai...

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Autores principales: Yan, Dewen, Zhu, Danyang, Zhao, Xiumin, Su, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769549/
https://www.ncbi.nlm.nih.gov/pubmed/29371831
http://dx.doi.org/10.1186/s12935-018-0505-3
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author Yan, Dewen
Zhu, Danyang
Zhao, Xiumin
Su, Jun
author_facet Yan, Dewen
Zhu, Danyang
Zhao, Xiumin
Su, Jun
author_sort Yan, Dewen
collection PubMed
description BACKGROUND: Autophagy is a cell degradation pathway that eliminates damaged or unwanted proteins and organelles. Autophagy protects cells from chemotherapeutic agents by scavenging damaged mitochondria. METHODS: Plasmid transfection and shRNA were used to regulate SHP-2 expression. Annexin V/PI staining were employed to analysis apoptosis. Flow cytometry was used to analyse intracellular calcium level and ROS. Immunofluorescence was used to detect mitochondria membrane potential, autophagy and Parkin translocation. RESULTS: In cervical cancer, we found that SHP-2 suppressed apoptosis induced by Oxaliplatin and 5-FU. Further studies have found that SHP-2 protects against mitochondrial damage. This role of SHP-2 is associated with the activation of autophagy. In addition, SHP-2 degraded impaired mitochondria dependent on the ubiquitin ligase function of Parkin. CONCLUSIONS: These results suggest that SHP-2 inhibits the apoptosis induced by chemotherapeutic drugs through activating autophagy to degrade damaged mitochondria and ubiquitin ligase Parkin involved in SHP-2 induced autophagy.
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spelling pubmed-57695492018-01-25 SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer Yan, Dewen Zhu, Danyang Zhao, Xiumin Su, Jun Cancer Cell Int Primary Research BACKGROUND: Autophagy is a cell degradation pathway that eliminates damaged or unwanted proteins and organelles. Autophagy protects cells from chemotherapeutic agents by scavenging damaged mitochondria. METHODS: Plasmid transfection and shRNA were used to regulate SHP-2 expression. Annexin V/PI staining were employed to analysis apoptosis. Flow cytometry was used to analyse intracellular calcium level and ROS. Immunofluorescence was used to detect mitochondria membrane potential, autophagy and Parkin translocation. RESULTS: In cervical cancer, we found that SHP-2 suppressed apoptosis induced by Oxaliplatin and 5-FU. Further studies have found that SHP-2 protects against mitochondrial damage. This role of SHP-2 is associated with the activation of autophagy. In addition, SHP-2 degraded impaired mitochondria dependent on the ubiquitin ligase function of Parkin. CONCLUSIONS: These results suggest that SHP-2 inhibits the apoptosis induced by chemotherapeutic drugs through activating autophagy to degrade damaged mitochondria and ubiquitin ligase Parkin involved in SHP-2 induced autophagy. BioMed Central 2018-01-15 /pmc/articles/PMC5769549/ /pubmed/29371831 http://dx.doi.org/10.1186/s12935-018-0505-3 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Yan, Dewen
Zhu, Danyang
Zhao, Xiumin
Su, Jun
SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer
title SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer
title_full SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer
title_fullStr SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer
title_full_unstemmed SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer
title_short SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer
title_sort shp-2 restricts apoptosis induced by chemotherapeutic agents via parkin-dependent autophagy in cervical cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769549/
https://www.ncbi.nlm.nih.gov/pubmed/29371831
http://dx.doi.org/10.1186/s12935-018-0505-3
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