Matrix crosslinking forces tumor progression by enhancing integrin signaling.
Matrix crosslinking forces tumor progression by enhancing integrin signaling.
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DOI：
10.1016/j.cell.2009.10.027
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发表时间：
2009-11-25
期刊：
影响因子：
64.5
通讯作者：
Weaver VM
中科院分区：
文献类型：
--
作者：
Levental KR;Yu H;Kass L;Lakins JN;Egeblad M;Erler JT;Fong SF;Csiszar K;Giaccia A;Weninger W;Yamauchi M;Gasser DL;Weaver VM
肿瘤的特征在于细胞外基质（ECM）重塑和硬化。ECM重塑对癌症的重要性是值得赞赏的;硬化的相关性不太清楚。我们发现，乳腺肿瘤发生伴随着胶原交联，ECM硬化和增加局灶性粘连。诱导胶原交联硬化ECM，促进局灶性粘连，增强PI 3激酶（PI 3 K）活性，并诱导癌基因启动的上皮细胞的侵袭。抑制整联蛋白信号转导抑制癌前上皮细胞侵入硬化、交联的ECM，强迫整联蛋白聚集促进局灶性粘连，增强PI 3 K信号转导并诱导癌前上皮细胞侵入。一致地，减少赖氨酰氧化酶介导的胶原交联防止MMTV-Neu诱导的纤维化，降低局灶性粘连和PI 3 K活性，阻止恶性肿瘤并降低肿瘤发生率。这些数据显示胶原交联如何调节组织纤维化和硬度，以迫使局灶性粘连、生长因子信号传导和乳腺癌。
Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The importance of ECM remodeling to cancer is appreciated; the relevance of stiffening is less clear. We found that breast tumorigenesis is accompanied by collagen crosslinking, ECM stiffening and increased focal adhesions. Inducing collagen crosslinking stiffened the ECM, promoted focal adhesions, enhanced PI3 Kinase (PI3K) activity, and induced the invasion of an oncogene-initiated epithelium. Inhibiting integrin signaling repressed the invasion of a premalignant epithelium into a stiffened, crosslinked ECM, and forced integrin clustering promoted focal adhesions, enhanced PI3K signaling and induced the invasion of a premalignant epithelium. Consistently, reducing lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy and lowered tumor incidence. These data show how collagen crosslinking can modulate tissue fibrosis and stiffness to force focal adhesions, growth factor signaling and breast malignancy.
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影响因子：
3.7
作者：
Bondareva A;Downey CM;Ayres F;Liu W;Boyd SK;Hallgrimsson B;Jirik FR
通讯作者：
Jirik FR
DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
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通讯作者：
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10.5
作者：
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通讯作者：
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21.3
作者：
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影响因子：
4.8
作者：
Atsawasuwan, Phimon;Mochida, Yoshiyuki;Yamauchi, Mitsuo
通讯作者：
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