CD44-mediated oncogenic signaling and cytoskeleton activation during mammary tumor progression
CD44-mediated oncogenic signaling and cytoskeleton activation during mammary tumor progression
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DOI：
10.1023/a:1011371523994
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发表时间：
2001-07-01
影响因子：
2.5
通讯作者：
Bourguignon, LYW
中科院分区：
文献类型：
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作者：
Bourguignon, LYW
CD 44是透明质酸（HA）（3）受体，属于跨膜糖蛋白家族，以几种亚型存在。某些CD 44亚型的细胞表面表达与乳腺癌的进展和预后密切相关。许多血管生成因子（例如，VEGF和FGF-2）和基质降解酶（MMP）与CD 44亚型紧密复合，表明它们参与乳腺肿瘤细胞侵袭和迁移所需的致癌信号的发生。最重要的是，细胞外基质组分（例如，HA）与细胞的结合触发CD 44同种型的胞质结构域结合其独特的下游效应物（例如，细胞骨架蛋白锚蛋白或各种致癌信号分子-Tiam 1、RhoA激活的ROK、c-Src激酶和p185（HER 2））并协调细胞内信号通路（例如，Rho/Ras信号传导和受体连接/非受体连接酪氨酸激酶途径），导致多种细胞功能（例如，肿瘤细胞生长、迁移和侵袭）和乳腺肿瘤进展。
CD44, a hyaluronan (HA)(3) receptor, belongs to a family of transmembrane glycoproteins which exists as several isoforms. Cell surface expression of certain CD44 isoforms is closely correlated with the progression and prognosis of breast cancers. A number of angiogenic factors (e.g., VEGF and FGF-2) and matrix degrading enzymes (MMPs) are tightly complexed with CD44 isoforms, suggesting that they are involved in the onset of oncogenic signals required for breast tumor cell invasion and migration. Most importantly, interaction of extracellular matrix components (e.g., HA) with cells triggers the cytoplasmic domain of CD44 isoforms to bind its unique downstream effectors (e.g., the cytoskeletal protein ankyrin or various oncogenic signaling molecules-Tiam1, RhoA-activated ROK, c-Src kinase and p185(HER2)) and to coordinate intracellular signaling pathways (e.g., Rho/Ras signaling and receptor-linked/non-receptor-linked tyrosine kinase pathways), leading to a concomitant onset of multiple cellular functions (e.g., tumor cell growth, migration and invasion) and breast tumor progression.