CD44 Regulates Pancreatic Cancer Invasion through MT1-MMP

被引：77

作者：

Jiang, Wei ^{[1
]}

Zhang, Yaqing ^{[1
]}

Kane, Kevin T. ^{[1
]}

Collins, Meredith A. ^{[2
]}

Simeone, Diane M. ^{[1
,3
]}

di Magliano, Marina Pasca ^{[1
,2
,4
]}

Nguyen, Kevin Tri ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Programin Cell & Mol Biol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA

来源：

MOLECULAR CANCER RESEARCH | 2015年 / 13卷 / 01期

关键词：

STEM-CELLS; DUCTAL ADENOCARCINOMA; GROWTH; KRAS(G12D); SNAIL1; MICE;

D O I：

10.1158/1541-7786.MCR-14-0076

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic cancer is one of the deadliest human malignancies due to its early metastatic spread and resistance to therapy. The mechanisms regulating pancreatic cancer metastasis are so far poorly understood. Here, using both in vitro and in vivo approaches, it is demonstrated that CD44, a transmembrane glycoprotein expressed on a subset of pancreatic cancer cells, is required for the induction of epithelial-mesenchymal transition (EMT) and the activation of an invasive program in pancreatic cancer. Mechanistically, the transcription factor Snail1 (SNAI1), a regulator of the EMT program, is a downstream target of CD44 in primary pancreatic cancer cells and regulates membrane bound metalloproteinase (MMP14/MT1-MMP) expression. In turn, MT1-MMP expression is required for pancreatic cancer invasion. Thus, these data establish the CD44-Snail-MMP axis as a key regulator of the EMT program and of invasion in pancreatic cancer.

引用

页码：9 / 15

页数：7

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