摘要：二氢嘧啶酶样蛋白3 (dihydropyrimidinase-like 3,DPYSL3)又称塌陷反应调节蛋白4 (collapse response mediator protein 4,CRMP4),是一种在神经系统中高表达的胞质磷蛋白。其不仅参与细胞伪足中肌动蛋白的组成,也用于组装细胞骨架,还与细胞上皮-间质转化(epithelial-mesenchymal transition,EMT)过程有关,这些特性可能与肿瘤增殖与转移功能有关。近年来有研究表明,DPYSL3参与多种癌细胞的增殖与侵袭过程,例如前列腺癌、膀胱癌、胃癌与肝癌等。然而,DPYSL3在不同肿瘤中的表达与预后存在明显的异质性。因此,进行DPYSL3在肿瘤表达水平的研究有望成为在不同肿瘤恶性程度与诊断过程中的生物标志物,从而提高肿瘤诊断率与患者预后水平。本文对DPYSL3在不同肿瘤中的表达、生物学功能及其对肿瘤的诊断、治疗及预后价值进行总结与探索,为肿瘤研究提供新思路。

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近年来，肿瘤生物学功能的研究一直处于肿瘤研究的前沿。细胞骨架动力学一直是支持许多细胞基本过程的重要现象，且在肿瘤发生发展中发挥重要作用^[1]。细胞骨架是一个复杂的动态网络，由高度有序的交联丝构成，在细胞形态维持、动力、分裂和细胞内运输等基本细胞过程的控制中起着关键作用^[2]。该功能与肿瘤形成密切相关，可促进其异常增殖，表现出不适当的迁移和侵入特征。在实体肿瘤中，细胞骨架与肿瘤特征间的联系已被广泛研究^[3]。经研究发现，许多基因参与到细胞骨架的形成中，其中，二氢嘧啶酶样蛋白3(dihydropyrimidinase-like3,DPYSL3)又称塌陷反应调节蛋白4(collapseresponse mediator protein 4,CRMP4),是最常见的参与细胞骨架形成的基因之一，该基因最初发现于中枢神经系统中，其功能为介导神经元突起的生长发育过程，并作为一种潜在治疗靶点用于治疗神经系统损伤与相关疾病^[4-5]。但近年来有研究得知，DPYSL3与肿瘤的发生发展有着密切关系，且在不同肿瘤中DPYSL3的表达及预后存在异质性^[6]。因此，通过明确DPYSL3与不同肿瘤表达水平间的关系，可为肿瘤的诊断、治疗及预后提供价值，进而为肿瘤相关研究提供理论基础及新思路。本文就DPYSL3结构、生物学功能、分布、调控机制及其在不同肿瘤中表达水平作一综述。

1 DPYSL3结构及其生物学功能

2 DPYSL3的分布

3 DPYSL3在肿瘤中的表达

3.1 前列腺癌  

3.2 胃癌

3.3 胰腺癌

3.4 神经母细胞瘤

3.5 胶质母细胞瘤

3.6 肺癌

3.7 尿路上皮癌

3.8 肝细胞癌

3.9 结直肠癌

4 展望与总结

DPYSL3作为一种在神经系统中高表达的胞质磷蛋白，近年来研究发现其在机体内多种肿瘤的表达水平、生物学功能与预后影响方面中存在差异。尽管对DPYSL3的研究已经取得了一些成果，但由于DPYSL3在不同阶段与微环境中可能有不同的表达和功能，其作用机制在很大程度上仍是未知的。本课题组希望进一步研究能够揭示DPYSL3在恶性肿瘤中的作用机制，为肿瘤的治疗提供新的思路。

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