Control of cell cycle progression by fibronectin matrix architecture
Control of cell cycle progression by fibronectin matrix architecture
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DOI：
10.1074/jbc.273.40.25533
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发表时间：
1998-10-02
影响因子：
4.8
通讯作者：
Schwarzbauer, JE
中科院分区：
文献类型：
--
作者：
Sechler, JL;Schwarzbauer, JE
肿瘤的发育模式和分化、实质细胞功能的维持以及肿瘤的大小、形状和侵袭性都是由细胞与细胞外基质的相互作用协调的。在这里，我们表明纤维连接蛋白（FN）基质的纤维结构编码必要的调节信号，并通过基质结构的变化控制细胞增殖和信号传导。由天然FN合成的基质刺激细胞生长。相反，含有所有已知细胞结合基序但形成结构不同的基质的FN突变体（FN Delta III1-7）抑制了从G(0)/G(1)向S期的进展。此外，FN Delta III1-7抑制了天然FN的刺激能力，诱导pp125（FAK）不同程度的酪氨酸磷酸化。通过阻断基质原纤维的形成，消除了对细胞生长的差异影响。因此，改变基质结构为控制细胞增殖提供了一种新的途径。
Developmental patterning and differentiation, maintenance of parenchymal cell function, and the size, shape, and invasiveness of tumors are all orchestrated by cell interactions with the extracellular matrix. Here we show that the fibrillar structure of fibronectin (FN) matrix encodes essential regulatory cues and controls cell proliferation and signaling through changes in matrix architecture. A matrix assembled from native FN stimulated cell growth. In contrast, a mutant FN (FN Delta III1-7) that contains all known cell binding motifs but forms a structurally distinct matrix inhibited progression from G(0)/G(1) into S phase. Furthermore, FN Delta III1-7 suppressed the stimulatory capacity of native FN and induced different levels of tyrosine phosphorylation of pp125(FAK). The differential effects on cell growth were ablated by blocking formation of matrix fibrils. Thus, modification of matrix architecture provides a novel approach to control cell proliferation.