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来自康奈尔大学的研究人员发现,大块糖萼(覆盖细胞表面的一个糖蛋白/多糖层)是转移性肿瘤细胞的一个特征,并指出糖萼及其分子组分是以使跨膜受体信号传导正常化为目的的治疗干预的有吸引力的目标。

                                                                                                                                                                         -2014年6月25日《自然》

 

 

中文翻译


【题目】细胞糖萼能诱导整合素介导的癌细胞生存

【译文】恶性肿瘤与组成细胞表面糖萼的聚糖和糖蛋白表达的改变有关。为此,我们构建了一个糖蛋白表达谱,表明了大块糖萼表达的上调是转移性肿瘤的一个特征。计算机模型预测,这些糖蛋白会影响跨膜受体的空间结构和功能。我们在大块糖萼中增加整合素的粘附和信号来判断其是否能促进人属肿瘤细胞的表型从而来检验这个预测。我们的结果表明,大块糖萼有利于输送活性信号的整合素簇集在一起,这种改变使得整合素与环境中不依赖肌动球蛋白收缩性的蛋白质支架结合。在非转化的乳腺细胞中,大块糖萼的表达能促进整合素装配,能够更有效地通过整合素接受细胞的生存信号。临床研究显示,大块糖萼在来自侵袭性乳腺癌患者的循环肿瘤细胞上大量表达。这些发现表明,糖萼是一个可以通过机械地增强细胞表面受体功能促进肿瘤细胞转移的一个特征。

英文原稿


[Title]: The cancer glycocalyx mechanically primes integrin-mediated growth and survival

[Authors]Matthew J. Paszek, Christopher C. DuFort, Olivier Rossier, Russell Bainer, Janna K. Mouw, Kamil Godula,Jason E. Hudak, Jonathon N. Lakins, Amanda C. Wijekoon, Luke Cassereau, Matthew G. Rubashkin, Mark J. Magbanua,Kurt S. Thorn, Michael W. Davidson, Hope S. Rugo, John W. Park, Daniel A. Hammer, Gre ´gory Giannone,Carolyn R. Bertozzi & Valerie M. Weaver

[Abstract]: Malignancy is associated with altered expression of glycans and glycoproteins that contribute to the cellular glycocalyx. We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. We tested this prediction by investigating whether bulky glycoproteins in the glycocalyx promote a tumour phenotype in human cells by increasing integrin adhesion and signalling. Our data revealed that a bulky glycocalyx facilitates integrin clustering by funnelling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Expression of large tumourassociated glycoproteins in non-transformed mammary cells promotedfocal adhesion assembly and facilitated integrindependent growth factor signalling to support cell growth and survival. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. Thus, a bulky glycocalyx is a feature of tumour cells that could foster m etastasis by mechanically enhancing cell-surface receptor function.

原文地址

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13535.html

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本文链接: http://www.bioku.cn/201406/nature-2014-06-25-the-cancer-glycocalyx-mechanically-primes-integrin-mediated-growth-and-survival/
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