文章：

鳞状细胞癌中的层粘连蛋白332

Laminin 332 in squamous-cell carcinoma

原文发布日期：2007-05-01

DOI: 10.1038/nrc2089

类型: Review Article

开放获取: 否

要点：

1. Laminin 332, a large multidomain molecule involved in cell adhesion and matrix assembly, is a prominent component of squamous-cell carcinoma (SCC) extracellular matrix. The levels of laminin 332 expression in SCC tumours correlate with tumour invasion and patient prognosis.
2. Proteolytic processing of the γ2 and α3 chains of laminin 332 has been linked to cell migration and invasion. Members of the astacin family process the γ2chain, and various enzymes, including astacin enzymes, matrix metalloproteinase 2 (MMP2), MT1-MMP and plasmin process the α3 chain.
3. The association of cells with laminin 332 occurs through α3β1 integrin in focal adhesions and α6β4 in stable anchoring contacts, which contain an assembly of hemidesmosome proteins.
4. The binding of laminin 332 to β1 integrin promotes RHOA GTPase-driven non-directional migration, whereas the binding of laminin 332 to β4 integrin promotes RAC1 GTPase-driven directional migration.
5. An in vivo model of human SCC tumour development has shown the essential role of laminin-332, α6β4 integrin and collagen VII, which associate and drive SCC tumorigenesis through phosphatidylinositol-3 kinase (PI3K) activation.
6. The laminin G4–5 domain is a proteolytic product of laminin 332 that promotes laminin 332 deposition, is expressed in healing wounds and might have a role in SCC formation.
7. The binding of collagen VII or the proteolytic processing of laminin 332 might regulate epidermal growth factor receptor (EGFR) activation, which functions in concert with α6β4 integrin signalling to drive SCC tumorigenesis.

要点翻译：

1. 层粘连蛋白332是一种参与细胞粘附和基质组装的大分子多域蛋白，是鳞状细胞癌（SCC）细胞外基质的重要组成成分。其在SCC肿瘤中的表达水平与肿瘤侵袭及患者预后密切相关。
2. 层粘连蛋白332的γ2链和α3链的蛋白水解处理与细胞迁移和侵袭相关。虾红素家族成员可处理γ2链，而多种酶（包括虾红素酶、基质金属蛋白酶2、MT1-MMP和纤溶酶）则参与α3链的加工。
3. 细胞与层粘连蛋白332的结合通过黏着斑中的α3β1整合素和稳定锚定接触中的α6β4整合素实现，后者包含半桥粒蛋白的组装。
4. 层粘连蛋白332与β1整合素的结合促进RHOA GTP酶驱动的非定向迁移，而与β4整合素的结合则促进RAC1 GTP酶驱动的定向迁移。
5. 人体SCC肿瘤发展的体内模型显示，层粘连蛋白332、α6β4整合素和VII型胶原通过激活磷脂酰肌醇-3激酶（PI3K）相互关联并共同驱动SCC肿瘤发生，具有重要作用。
6. 层粘连蛋白G4–5结构域是层粘连蛋白332的蛋白水解产物，可促进层粘连蛋白332沉积，在愈合伤口中表达，并可能在SCC形成中发挥作用。
7. VII型胶原的结合或层粘连蛋白332的蛋白水解处理可能调节表皮生长因子受体（EGFR）的激活，该受体与α6β4整合素信号传导协同作用，共同驱动SCC肿瘤发生。

英文摘要：

Basement membranes can be a barrier to tumour growth, but basement membrane molecules, including laminins, are also important autocrine factors produced by cancers to promote tumorigenesis. Many studies have shown the importance of laminin 332 (previously known as laminin 5) in this process, especially in squamous cell carcinoma. Through interactions with several cell-surface receptors (including α6β4 and α3β1 integrins, epidermal growth factor receptor and syndecan 1) and other basement membrane components (including type VII collagen), laminin 332 drives tumorigenesis through phosphatidylinositol-3 kinase (PI3K) and RAC1 activation, promoting tumour invasion and cell survival. The extracellular interactions of laminin 332 appear amenable to antibody-mediated therapies.

摘要翻译： 

基底膜可成为肿瘤生长的屏障，但基底膜分子（包括层粘连蛋白）也是癌症产生的重要自分泌因子，可促进肿瘤发生。许多研究已证明层粘连蛋白 332（旧称层粘连蛋白 5）在此过程中至关重要，尤其在鳞状细胞癌中。通过与多种细胞表面受体（包括 α6β4 和 α3β1 整合素、表皮生长因子受体及 syndecan 1）以及其它基底膜成分（如 VII 型胶原）相互作用，层粘连蛋白 332 激活磷脂酰肌醇-3 激酶（PI3K）和 RAC1，促进肿瘤侵袭和细胞存活。层粘连蛋白 332 的细胞外相互作用似乎适合抗体介导的治疗。

原文链接：

Laminin 332 in squamous-cell carcinoma