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

Open Access 01-12-2018 | Primary Research

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

Authors: Dewen Yan, Danyang Zhu, Xiumin Zhao, Jun Su

Published in: Cancer Cell International | Issue 1/2018

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Abstract

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.
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
2.
Castellsague X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol. 2008;110(3 Suppl 2):S4–7.CrossRefPubMed
3.
Clifford GM, Smith JS, Plummer M, Munoz N, Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer. 2003;88(1):63–73.CrossRefPubMedPubMedCentral
4.
Reinhardt MJ, Ehritt-Braun C, Vogelgesang D, Ihling C, Hogerle S, Mix M, Moser E, Krause TM. Metastatic lymph nodes in patients with cervical cancer: detection with MR imaging and FDG PET. Radiology. 2001;218(3):776–82.CrossRefPubMed
5.
Bunz F. Thymidylate synthase and 5-fluorouracil: a cautionary tale. Cancer Biol Ther. 2008;7(7):995–6.CrossRefPubMed
6.
Yang YC, Chao KS, Lin CP, Chen YY, Wang KL, Chen YJ. Oxaliplatin regulates DNA repair responding to ionizing radiation and enhances radiosensitivity of human cervical cancer cells. Int J Gynecol Cancer 2009;19(4):782–6.
7.
Giorgio M, Migliaccio E, Orsini F, Paolucci D, Moroni M, Contursi C, Pelliccia G, Luzi L, Minucci S, Marcaccio M, et al. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell. 2005;122(2):221–33.CrossRefPubMed
8.
9.
Ly JD, Grubb DR, Lawen A. The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis. 2003;8(2):115–28.CrossRefPubMed
10.
Ding WX, Ni HM, Li M, Liao Y, Chen X, Stolz DB, Dorn GW 2nd, Yin XM. Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J Biol Chem. 2010;285(36):27879–90.CrossRefPubMedPubMedCentral
11.
Neel BG, Gu H, Pao L. The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci. 2003;28(6):284–93.CrossRefPubMed
12.
Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007;7(8):573–84.CrossRefPubMed
13.
Peng X, Gong F, Chen Y, Jiang Y, Liu J, Yu M, Zhang S, Wang M, Xiao G, Liao H. Autophagy promotes paclitaxel resistance of cervical cancer cells: involvement of Warburg effect activated hypoxia-induced factor 1-alpha-mediated signaling. Cell Death Dis. 2014;5:e1367.CrossRefPubMedPubMedCentral
14.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.CrossRefPubMed
15.
Sausgruber N, Coissieux MM, Britschgi A, Wyckoff J, Aceto N, Leroy C, Stadler MB, Voshol H, Bonenfant D, Bentires-Alj M. Tyrosine phosphatase SHP2 increases cell motility in triple-negative breast cancer through the activation of SRC-family kinases. Oncogene. 2015;34(17):2272–8.CrossRefPubMed
16.
Kim C, Baek SH, Um JY, Shim BS, Ahn KS. Resveratrol attenuates constitutive STAT3 and STAT5 activation through induction of PTPepsilon and SHP-2 tyrosine phosphatases and potentiates sorafenib-induced apoptosis in renal cell carcinoma. BMC Nephrol. 2016;17:19.CrossRefPubMedPubMedCentral
17.
Eiyama A, Okamoto K. PINK1/Parkin-mediated mitophagy in mammalian cells. Curr Opin Cell Biol. 2015;33:95–101.CrossRefPubMed
18.
Komatsu M, Kageyama S, Ichimura Y. p62/SQSTM1/A170: physiology and pathology. Pharmacol Res. 2012;66(6):457–62.CrossRefPubMed
Metadata
Title
SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer
Authors
Dewen Yan
Danyang Zhu
Xiumin Zhao
Jun Su
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/s12935-018-0505-3

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