CD44 regulates pancreatic cancer invasion through MT1-MMP.
CD44 regulates pancreatic cancer invasion through MT1-MMP.
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DOI：
10.1158/1541-7786.mcr-14-0076
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Nguyen KT
中科院分区：
文献类型：
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作者：
Jiang W;Zhang Y;Kane KT;Collins MA;Simeone DM;di Magliano MP;Nguyen KT
胰腺癌是最致命的人类恶性肿瘤之一，由于其早期转移扩散和耐药治疗。调节胰腺癌转移的机制迄今知之甚少。在这里，使用体外和体内方法，它表明，CD 44，胰腺癌细胞的子集上表达的跨膜糖蛋白，是需要诱导上皮间质转化（EMT）和胰腺癌中的侵入性程序的激活。从机制上讲，转录因子Snail 1（SNAI 1）是EMT程序的调节因子，是原发性胰腺癌细胞中CD 44的下游靶标，并调节膜结合金属蛋白酶（MMP 14/MT 1-MMP）表达。反过来，MT 1-MMP表达是胰腺癌侵袭所必需的。因此，这些数据确立了CD 44-Snail-MMP轴作为胰腺癌EMT程序和侵袭的关键调节因子。(135)这项研究为CD 44和MT 1-MMP作为胰腺癌的治疗靶点奠定了基础，对于胰腺癌，小分子或生物抑制剂是可用的。
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. (135) This study sets the stage for CD44 and MT1-MMP as therapeutic targets in pancreatic cancer, for which small molecule or biologic inhibitors are available.