Dalvi Nafisa, Thomas Gareth J, Marshall John F, Morgan Mark, Bass Rosemary, Ellis Vincent, Speight Paul M, Whawell Simon A
Department of Oral Pathology, Eastman Dental Institute for Oral Health Care Sciences, University College London, London WC1X 8LD, UK.
Biochem Biophys Res Commun. 2004 Apr 23;317(1):92-9. doi: 10.1016/j.bbrc.2004.02.178.
Over-expression of components of the urokinase system is well documented in cancer and is thought to enable tumour cells to migrate and invade. Changes in integrin expression are also a common feature of tumours and have been linked to changes in protease activity. It has been shown that the alphavbeta6 integrin is neo-expressed in a number of epithelial carcinomas and in wound healing situations. We therefore investigated whether alphavbeta6 is able to modulate a key regulator of proteolysis, the urokinase receptor. We report that epithelial cells expressing full-length alphavbeta6 exhibit decreased urokinase receptor expression and function. Furthermore, this novel modulation requires the C-terminal 11 amino acids of the cytoplasmic tail of the beta6 integrin subunit. Cells expressing alphavbeta3, however, did not affect urokinase receptor expression. De novo expression of beta6 by melanoma cells and beta3 by epithelial cells did not influence urokinase receptor expression or function, suggesting that modulation of urokinase system is both integrin subunit and cell-specific.
尿激酶系统各组分的过表达在癌症中已有充分记载，并且被认为能使肿瘤细胞迁移和侵袭。整合素表达的变化也是肿瘤的一个常见特征，并且与蛋白酶活性的变化有关。研究表明，αvβ6整合素在多种上皮癌和伤口愈合情况下会重新表达。因此，我们研究了αvβ6是否能够调节蛋白水解的关键调节因子——尿激酶受体。我们报告称，表达全长αvβ6的上皮细胞表现出尿激酶受体表达和功能降低。此外，这种新的调节需要β6整合素亚基细胞质尾的C末端11个氨基酸。然而，表达αvβ3的细胞并未影响尿激酶受体的表达。黑色素瘤细胞中β6的从头表达以及上皮细胞中β3的从头表达均未影响尿激酶受体的表达或功能，这表明尿激酶系统的调节具有整合素亚基和细胞特异性。
