Exp Mol Med.  2011 May;43(5):291-297. 10.3858/emm.2011.43.5.030.

PAUF promotes adhesiveness of pancreatic cancer cells by modulating focal adhesion kinase

• Lee Y
• Kim SJ
• Min HJ
• Jo JY
• Park EH
• Koh SS

• KMID: 1009968
• DOI: http://doi.org/10.3858/emm.2011.43.5.030

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.

Keyword

adhesion; anoikis; FAK; PAUF; pancreatic cancer; signaling

MeSH Terms

Anoikis/genetics
Cell Line, Tumor
Focal Adhesion Protein-Tyrosine Kinases/*metabolism
Focal Adhesions/genetics/*metabolism
Humans
Lectins/genetics/*metabolism
Pancreatic Neoplasms/enzymology/genetics/*metabolism
Proto-Oncogene Proteins pp60(c-src)/metabolism
Signal Transduction/genetics