The tyrosine phosphatase PTPRO sensitizes colon cancer cells to anti-EGFR therapy through activation of SRC-mediated EGFR signaling

摘要: Inappropriate activation of epidermal growth factor receptor (EGFR) plays a causal role in many cancers including colon cancer. The EGFR by phosphorylation is balanced kinase and protein tyrosine phosphatase activities. However, the mechanisms negative regulation phosphatases remain largely unexplored. Our previous results indicate that type O (PTPRO) down-regulated subset colorectal cancer (CRC) patients with poor prognosis. Here we identified PTPRO as negatively regulates SRC directly dephosphorylating Y416 site. triggered down-regulation induces both at Y845 c-CBL ubiquitin ligase Y731. Increased promotes its activity, whereas enhanced triggers degradation promoting stability. Importantly, hyperactivation SRC/EGFR signaling loss leads to high resistance inhibitors. not only highlight contribution but also suggest tumors low expression may be therapeutically targetable anti-SRC therapies.