CD26 regulates p38 mitogen-activated protein kinase-dependent phosphorylation of integrin β1, adhesion to extracellular matrix, and tumorigenicity of T-anaplastic large cell lymphoma karpas 299
CD26 regulates p38 mitogen-activated protein kinase-dependent phosphorylation of integrin β1, adhesion to extracellular matrix, and tumorigenicity of T-anaplastic large cell lymphoma karpas 299
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DOI：
10.1158/0008-5472.can-05-0647
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发表时间：
2005-08-01
期刊：
影响因子：
11.2
通讯作者：
Dang, NH
中科院分区：
文献类型：
--
作者：
Sato, T;Yamochi, T;Dang, NH
CD26 是一种在 T 细胞生物学中发挥关键作用的抗原，在选定的侵袭性 T 细胞恶性肿瘤亚群中表达。为了阐明 CD26 在肿瘤行为中的作用，我们检查了通过小干扰 RNA 转染 T 间变性大细胞淋巴瘤 Karpas 299 来消除 CD26 的效果。我们发现，所得 CD26 消除的克隆失去了粘附核连蛋白和 I 型胶原蛋白的能力。由于抗整合素 β(1) 阻断抗体也阻止了 Karpas 299 与纤连蛋白和 I 型胶原蛋白的结合，因此我们随后评估了CD26-整合素β(1) 关联。 CD26 耗竭不会降低整合素 β(1) 表达，但会导致整合素 β(1) 和 p38 丝裂原激活蛋白激酶 (MAPK) 去磷酸化。此外，我们的数据显示p38MAPK抑制剂SB203580使整合素β(1)去磷酸化，并且抗CD26抗体202.36的结合使Karpas 299上的p38MAPK和整合素β(1)去磷酸化，导致细胞与细胞外基质的粘附丧失，表明CD26通过整合素的p38MAPK依赖性磷酸化来介导细胞粘附贝塔（1）。最后，体内实验表明 CD26 的消耗与转化能力的丧失和更高的存活率相关。因此，我们的研究结果表明 CD26 在肿瘤发展中发挥着重要作用，并且可能是选定肿瘤的新治疗靶点。
CD26 is an antigen with key role in T-cell biology and is expressed on selected subsets of aggressive T-cell malignancies. To elucidate the role of CD26 in tumor behavior, we examine the effect of CD26 depletion by small interfering RNA transfection of T-anaplastic large cell lymphoma Karpas 299. We show that the resultant CD26-depleted clones lose the ability to adhere to ribronectin and collagen I. Because antiintegrin beta(1) blocking antibodies also prevent binding of Karpas 299 to fibronectin and collagen I, we then evaluate the CD26-integrin beta(1) association. CD26 depletion does not decrease integrin beta(1) expression but leads to dephosphorylation of both integrin beta(1) and p38 mitogen-activated protein kinase (MAPK). Moreover, our data showing that the p38MAPK inhibitor SB203580 dephosphorylates integrin beta(1) and that binding of the anti-CD26 antibody 202.36 dephosphorylates both p38MAPK and integrin beta(1) on Karpas 299, leading to loss of cell adhesion to the extracelhilar matrix, indicate that CD26 mediates cell adhesion through p38MAPKdependent phosphorylation of integrin beta(1). Finally, in vivo experiments show that depletion of CD26 is associated with loss of turnorigenicity and greater survival. Our findings hence suggest that CD26 plays an important role in tumor development and may be a novel therapeutic target for selected neoplasms.