Abstract
Pancreatic cancer is a notorious disease with a poor prognosis and low survival rates, which is due to limited advances in understanding of the molecular mechanism and inadequate development of effective treatment options over the decades. In previous studies, we demonstrated that a novel soluble protein named pancreatic adenocarcinoma up-regulated factor (PAUF) acts on tumor and immune cells and plays an important role in metastasis and progression of pancreatic cancer. Here we show that PAUF promotes adhesiveness of pancreatic cancer cells to various extracellular matrix (ECM). Our results further support a positive correlation of activation and expression of focal adhesion kinase (FAK), a key player in tumor cell metastasis and survival, with PAUF expression. PAUF-mediated adhesiveness was significantly attenuated upon blockade of the FAK pathway. Moreover, PAUF appeared to enhance resistance of pancreatic cancer cells to anoikis via modulation of FAK. Our results suggest that PAUF-mediated FAK activation plays an important role in pancreatic cancer progression.
Highlights
Pancreatic cancer, the fourth leading cause of cancer-induced mortality in both men and women, has an exceedingly poor prognosis, and is a major health issue in the developed world (Maitra and Hruban, 2008)
We investigated whether pancreatic adenocarcinoma up-regulated factor (PAUF) influences the adhesiveness of pancreatic cancer cells to extracellular matrix (ECM)
The effect of anti-PAUF on adhesiveness was relatively low in PAUF-knockdown pancreatic cancer cells than its control cells (Figure 1D). These results support the theory that PAUF promotes adhesiveness of pancreatic cancer cells to ECM in an autocrine manner
Summary
Pancreatic cancer, the fourth leading cause of cancer-induced mortality in both men and women, has an exceedingly poor prognosis, and is a major health issue in the developed world (Maitra and Hruban, 2008). PAUF acts in an autocrine manner to activate the ERK, JNK and AKT intracellular signaling cascades, resulting in increased expression of the genes involved in tumor progression and metastasis (Lee et al, 2010). PAUF interacts with the CXCR4-TLR2 complex and inhibits CXCR4-dependent TLR2-mediated NFκB activation in a paracrine manner (Park et al, 2011). These results suggest that PAUF enhances tumorigenic potential through facilitating tumor metastasis and escaping immuno-surveillance
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