The cancer glycocalyx mechanically primes integrin-mediated growth and survival.
The cancer glycocalyx mechanically primes integrin-mediated growth and survival.
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DOI：
10.1038/nature13535
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发表时间：
2014-07-17
期刊：
影响因子：
64.8
通讯作者：
Weaver, Valerie M.
中科院分区：
文献类型：
--
作者：
Paszek, Matthew J.;DuFort, Christopher C.;Rossier, Olivier;Bainer, Russell;Mouw, Janna K.;Godula, Kamil;Hudak, Jason E.;Lakins, Jonathon N.;Wijekoon, Amanda C.;Cassereau, Luke;Rubashkin, Matthew G.;Magbanua, Mark J.;Thorn, Kurt S.;Davidson, Michael W.;Rugo, Hope S.;Park, John W.;Hammer, Daniel A.;Giannone, Gregory;Bertozzi, Carolyn R.;Weaver, Valerie M.
恶性肿瘤与构成细胞糖萼的聚糖和糖蛋白的表达改变有关。我们构建了糖蛋白表达特征，揭示了转移性肿瘤上调大糖蛋白的表达。计算模型预测这些糖蛋白将影响跨膜受体的空间组织和功能。我们通过研究糖萼中的大糖蛋白是否通过增加整合素粘附和信号传导来促进人类细胞中的肿瘤表型，从而测试了这一预测。我们的数据显示，庞大的糖萼通过将活性整合素汇集到粘连中，并通过对基质结合的整合素施加张力来改变整合素状态，从而促进整合素聚集，而与肌动球蛋白的收缩性无关。未转化乳腺细胞中大的肿瘤相关糖蛋白的表达促进了粘着斑组装，并促进整合素依赖性生长因子信号传导以支持细胞生长和存活。临床研究表明，晚期疾病患者的循环肿瘤细胞大量表达大糖蛋白。因此，庞大的糖萼是肿瘤细胞的一个特征，可以通过机械增强细胞表面受体功能来促进转移。
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 tumour-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin-dependent 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 metastasis by mechanically enhancing cell-surface receptor function.
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影响因子：
21.3
作者：
Rossier, Olivier;Octeau, Vivien;Giannone, Gregory
通讯作者：
Giannone, Gregory
影响因子：
11.2
作者：
Magbanua MJ;Sosa EV;Roy R;Eisenbud LE;Scott JH;Olshen A;Pinkel D;Rugo HS;Park JW
通讯作者：
Park JW
影响因子：
78.5
作者：
Kufe, Donald W.
通讯作者：
Kufe, Donald W.
影响因子：
48
作者：
Manley, Suliana;Gillette, Jennifer M.;Lippincott-Schwartz, Jennifer
通讯作者：
Lippincott-Schwartz, Jennifer
影响因子：
14.8
作者：
Friedrichs, Jens;Helenius, Jonne;Muller, Daniel J.
通讯作者：
Muller, Daniel J.