Abstract
Pancreatic cancer has an extremely grim prognosis, with an overall 5-year survival rate less than 5%, as a result of its rapid metastasis and late diagnosis. To combat this disease, it is crucial to better understand the molecular mechanisms that contribute to its pathogenesis. Herein, we report that apoptosis signal-regulating kinase 1 (ASK1) is overexpressed in pancreatic cancer tissues and that its expression correlates with the histological grade of pancreatic cancer. The expression of ASK1 is also elevated in pancreatic cancer cell lines at both protein and mRNA levels. In addition, ASK1 promotes the proliferation and stimulates the tumorigenic capacity of pancreatic cancer cells. These functions of ASK1 are abrogated by pharmacological inhibition of its kinase activity or by introduction of a kinase-dead mutation, suggesting that the kinase activity of ASK1 is required for its role in pancreatic cancer. However, the alteration of ASK1 expression or activity does not significantly affect the migration or invasion of pancreatic cancer cells. Collectively, these findings reveal a critical role for ASK1 in the development of pancreatic cancer and have important implications for the diagnosis and treatment of this malignancy.
Highlights
Pancreatic cancer is a highly malignant disease that is a leading cause of cancer-associated deaths
To investigate whether apoptosis signal-regulating kinase 1 (ASK1) plays a role in pancreatic cancer tumorigenesis, we compared the expression of ASK1 in pancreatic cancer tissues and adjacent tissues by immunohistochemistry (Figure 1A, 1B)
More than 60% of cancer tissues showed high expression of ASK1, while only 40% of adjacent tissues showed high expression (Figure 1C). This differential staining pattern suggests that ASK1 is overexpressed in pancreatic cancer
Summary
Pancreatic cancer is a highly malignant disease that is a leading cause of cancer-associated deaths. Less than 5% of patients survive five years after diagnosis. Several tumor suppressor genes and oncogenes have been shown to be mutated in pancreatic cancer; for example, KRAS2, TP53, SMAD4, and other tumor-associated genes have been demonstrated to contribute to the pathogenesis of pancreatic cancer by promoting the expression of downstream genes and disrupting the cell cycle [3]. Despite this knowledge, a complete understanding of the underlying mechanisms that drive pancreatic cancer remains elusive. We currently lack biomarkers to diagnose this disease at an early stage and, thereby, improve the survival rate
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