CD147 promotes DNA damage response and gemcitabine resistance via targeting ATM/ATR/p53 and affects prognosis in pancreatic cancer.
The acquisition of chemoresistance is a major clinical challenge for pancreatic cancer (PC) treatment. Chemoresistance is largely attributed to aberrant DNA damage repair. However, the underlying mechanisms of chemoresistance in pancreatic cancer remain unclear. Here, we showed that CD147 was strongly correlated to DNA damage response (DDR) indices and poor ... prognosis in pancreatic ductal adenocarcinoma (PDAC) patients. CD147 knockdown or monoclonal antibodies improved the killing effects of gemcitabine in gemcitabine resistant cells, exhibiting reduced activation of ATM/p53. Moreover, we found the interaction of CD147 with ATM, ATR and p53, which was augmented in gemcitabine resistant cells. High CD147/p-ATM/p-ATR/p-p53 cytoplasmic expression associated with poor survival of PC patients. Our studies thus identify CD147 as a critical player in DDR programing that affects gemcitabine therapeutic outcomes of pancreatic cancer patients.
Mesh Terms:
Animals, Ataxia Telangiectasia Mutated Proteins, Basigin, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cytoplasm, DNA Damage, Deoxycytidine, Drug Resistance, Neoplasm, Gemcitabine, Genomic Instability, Humans, Mice, Pancreatic Neoplasms, Prognosis, Signal Transduction, Survival Analysis, Tumor Suppressor Protein p53
Animals, Ataxia Telangiectasia Mutated Proteins, Basigin, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cytoplasm, DNA Damage, Deoxycytidine, Drug Resistance, Neoplasm, Gemcitabine, Genomic Instability, Humans, Mice, Pancreatic Neoplasms, Prognosis, Signal Transduction, Survival Analysis, Tumor Suppressor Protein p53
Biochem Biophys Res Commun
Date: Jul. 12, 2020
PubMed ID: 32456796
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