부산대학교 도서관

Pancreatic cancer is arguably the deadliest cancer type. Patients are diagnosed at advanced stages at which point therapeutic intervention is rarely successful. To date, current treatments have not been clinically efficacious. The 5-year survival of pancreatic cancer patients remains dismal (4%) without treatment and only increases to 20% after chemotherapy. The development of clinical tools for early detection and risk prediction is key for improving patient outcome and quality of life. Here, we introduce the calciummodulating protein S100A10 as a novel biomarker in pancreatic cancer and a driver of pancreatic tumor growth and invasion. S100A10 belongs to the S100 family of Ca2+- binding proteins that have been linked to cell proliferation, Ca2+ homeostasis, cellular stress, apoptosis, differentiation etc. S100A10 is required for calcium homeostasis by regulating activity and surface translocation of the Ca2+ channels TRPV5 and TRPV6. We herein demonstrate that S100A10 mRNA and protein are overexpressed in human pancreatic tumors compared to the nearby normal ducts and non-ductal stroma. S100A10 mRNA expression was predictive of overall survival and recurrence-free survival across multiple pancreatic cancer patient cohorts. S100A10 expression was driven by promoter methylation and the oncogene KRAS. S100A10 knockdown resulted in decrease in TRPV5 expression and reduced invasiveness of pancreatic cancer cell lines. Additionally, S100A10 knockdown attenuates growth and metastatic burden of pancreatic tumor cells in vivo. In conclusion, these findings delineate, for the first time, the clinical and functional contribution of the calciummodulating protein S100A10 as a biomarker in pancreatic cancer. [ABSTRACT FROM AUTHOR]