Autophagy is a cell degradation pathway that eliminates damaged or unwanted proteins and organelles. Autophagy protects cells from chemotherapeutic agents by scavenging damaged mitochondria.
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.
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.
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.
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.
- SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent autophagy in cervical cancer
- BioMed Central
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