PAUF 通过调节粘着斑激酶促进胰腺癌细胞的黏附。
PAUF promotes adhesiveness of pancreatic cancer cells by modulating focal adhesion kinase.
机构信息
Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon.
出版信息
Exp Mol Med. 2011 May 31;43(5):291-7. doi: 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.
摘要
胰腺癌预后差、存活率低，是一种恶名昭著的疾病，这主要归咎于几十年来人们对其分子机制的了解有限，也未能开发出有效的治疗方法。在之前的研究中，我们证明了一种名为胰腺腺癌上调因子（PAUF）的新型可溶性蛋白作用于肿瘤细胞和免疫细胞，并在胰腺癌的转移和进展中发挥重要作用。在这里，我们发现 PAUF 可促进胰腺癌细胞与各种细胞外基质（ECM）的黏附。我们的结果进一步支持了粘着斑激酶（FAK）的激活和表达与 PAUF 表达之间的正相关，FAK 是肿瘤细胞转移和存活的关键参与者。FAK 通路被阻断后，PAUF 介导的黏附作用明显减弱。此外，PAUF 似乎通过调节 FAK 增强了胰腺癌细胞对失巢凋亡的抵抗能力。我们的研究结果表明，PAUF 介导的 FAK 激活在胰腺癌的进展中发挥重要作用。
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