Abstract
BackgroundAutophagy is a cell degradation pathway that eliminates damaged or unwanted proteins and organelles. Autophagy protects cells from chemotherapeutic agents by scavenging damaged mitochondria.MethodsPlasmid 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.ResultsIn 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.ConclusionsThese 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.
Highlights
Autophagy is a cell degradation pathway that eliminates damaged or unwanted proteins and organelles
SHP‐2 suppresses cervical cancer apoptosis induced by Oxaliplatin and 5‐FU Studies have shown that SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) expression is increased following HPV16/18 infection in cervical cancer
The above results show that SHP-2 suppresses cervical cancer apoptosis induced by Oxaliplatin and 5-FU
Summary
Autophagy is a cell degradation pathway that eliminates damaged or unwanted proteins and organelles. Autophagy protects cells from chemotherapeutic agents by scavenging damaged mitochondria. The third most common malignant tumor, is mainly caused by human papillomavirus (HPV) infection [1]. Over 99% of cervical cancer cases are a result of HPV infection [2], and of those about 70% are a result of infection with HPV16/18 [3]. Tumor metastasis is an important cause of death in cancer patients. In patients with cervical cancer, lymph node metastasis reduced 5-year overall survival rates, compared with patients without lymph node metastasis [4]. Pelvic and abdominal aortic lymph node metastasis is common in advanced cervical cancer patients.
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