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.
Keywords: Apoptosis; Autophagy; Mitochondria damage; Parkin; SHP-2.