MUC1 promotes glycolysis through inhibiting BRCA1 expression in pancreatic cancer

• 来源期刊: 中国天然药物
• 学科: 医学
• 年，卷（期）: 2020,（3）
• 页码范围: 178-185
• 页数: 8页
• 分类号: R965
• 语种: 英文
• DOI: 10.1016/S1875-5364(20)30019-4

摘要

Enhanced glucose metabolism is one of the hallmarks of pancreatic cancer.MUC 1,a transmembrane protein,is a global regulator of glucose metabolism and essential for progression of pancreatic cancer.To clarify the role of MUC 1 in glucose metabolism,we knocked out MUC1 in Capan-1 and CFPAC-1 cells.MUC1 knockout (KO) cells uptook less glucose and secreted less lactate with a much lower proliferating rate.The mRNA level of key enzymes in glycolysis also decreased significantly in MUC1 KO cells.We also observed increased expression of breast cancer type 1 susceptibility protein (BRCA 1) in MUC1 KO ceils.Since BRCA 1 has a strong inhibitory effect on glycolysis,we want to know whether the decreased glucose metabolism in MUC1 KO cells is due to increased BRCA1 expression.We treated wild type (WT) and MUC1 KO cells with BRCA1 inhibitor.BRCA1 inhibition significantly enhanced glucose uptake and lactate secretion in both WT and MUC l KO ceils.Expression of key enzymes in glycolysis also elevated after BRCA1 inhibition.Elevated glucose metabolism is known to facilitate cancer cells to gain chemoresistance.We treated MUC1 KO cells with gemcitabine and FOLFIRINOX in vitro and in vivo.The results showed that MUC1 KO sensitized pancreatic cancer cells to chemotherapy both in vitro and in vivo.In conclusion,we demonstrated that MUC 1 promotes glycolysis through inhibiting BRCA1 expression.MUC1 may be a therapeutic target in pancreatic cancer treatment.