摘要：癌症是目前威胁人类健康的最常见的疾病之一。越来越多的证据表明，癌症是一种人类基因组疾病。 因此，探究导致癌症的相关基因及其发病机制成为目前癌症治疗研究的热点。ADP-核糖基化因子 4c （ADPribosylation factor- like 4c，ARL4C） 属于三磷酸鸟苷 （guanosine triphosphate, GTP） 结合蛋白家族，在 1999年由 Jacobs等首次从人膀胱上皮细胞中检测到该分子 cDNA的全长编码序列。本文概述了 ARL4C分子结构 及生物学功能，同时总结了其在肺癌、结直肠癌、胃癌、胰腺癌、原发性人胶质母细胞瘤、卵巢癌、肾癌等肿瘤 中的研究进展。希望通过本文的概述，能够为研究 ARL4C与癌症的发生、发展的相关性及相关信号通路提供思 路，进而为肿瘤的治疗提供新的靶点以及预后标记物。

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张培志，崔子连，康维亭，等.ARL4C 的生物功能及其与肿瘤的相关性[J]. 泌尿外科杂志（电子版）,2023,15(1):82-87. DOI:10.20020/j.CNKI.1674-7410.2023.01.15

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癌症是目前威胁人类健康的最常见的疾病之 一，也是全球范围内导致人类死亡的第二大原因， 据统计，癌症每年造成超过 800万人死亡，并且在未来几十年中，癌症的发病率预计将增加 50%以上[1] 。 越来愈多的证据表明，癌症是一种人类基因组疾 病[2] ，因此，探究导致癌症的相关基因及其发病 机制，并以此为靶点进行基因治疗成为目前癌症 治疗研究的热点。ADP-核糖基化因子 （Arf） 样蛋 白 4c （ADP- ribosylation factor- like protein 4c， ARL4C） 作为三磷酸鸟苷 （guanosine triphosphate， GTP） 结合蛋白家族的成员，在 1999年由 Jacobs等 人首次从人膀胱上皮细胞中检测出其 cDNA 的全长 编码序列[3] 。其在细胞物质代谢及分子生物学功能方 面的作用已经被部分证实，并且，作为一种肿瘤相 关基因，ARL4C 与肺癌、结直肠癌、胃癌、睾丸 癌、黑色素瘤、原发性人胶质母细胞瘤、卵巢癌和 肾癌等肿瘤的相关性已经被证实。然而，ARL4C对 于其他肿瘤的发生、发展的作用还不甚了解。因此 现就 ARL4C本身分子特点及与肿瘤的相关性予以综 述，以期为研究 ARL4C与肿瘤的相关性及其潜在的 作用机制提供思路，进而为肿瘤的基因治疗提供新 的靶点以及预后标记物。

1 ARL4C 及其家族基因的研究进展

    1.1 ARL4C所属家族及其分布

    1.2 ARL4C 的分子结构及作用模式

2 ARL4C 分子生物学的研究

    2.1 ARL4C表达受到胆固醇的诱导并调节细胞内胆固醇的运输

    2.2 ARL7 与 α-微管蛋白相互作用并调节细胞内囊泡运输

    2.3 ARL4C 基因的表达促进上皮管状结构的形成

3 ARL4C 与不同肿瘤发生发展相关性研究

    3.1 ARL4C与肺癌及结肠癌的相关性

    3.2 ARL4C 与卵巢癌的相关性

    3.3 ARL4C 与原发性人类胶质母细胞瘤的相关性

    3.4 ARL4C 与胃肿瘤的相关性

    3.5 ARL4C 与 胰 腺 癌 的 相 关 性

    3.6 ARL4C 与肾癌的相关性

4 发展与展望

4 发展与展望

癌症一直是危及人类健康的最主要疾病之一。 虽然当前针对于癌症的治疗方式趋向于多样化，但 缺乏相关的早期诊断、肿瘤分级及判断预后的分子 生物标志物也导致大多数肿瘤的预后仍然较差。尽 管不同肿瘤在病理形态学和分子发生机制之间存在 较为广泛的差异，但其在肿瘤发生及发展过程中也 必然存在部分共性。小管发生 （Tubulogenesis） 是 许多上皮器官的基本形态发生过程。在这个发育过 程中，上皮细胞向周围的间充质组织迁移、增殖、 极化和分化，形成管状结构。尽管上皮组织结构在 出生后基本上是稳定的，但是上皮细胞在肿瘤发生 过程中重新获得了高度增殖和侵袭潜能。因此，必 须有一个共同的分子基础来协调参与上皮小管形成 和肿瘤发生的细胞行为。属于 GTP结合蛋白家族的 ARL4C 被确定为上皮管状结构发生的重要调节剂。 对于 ARL4C在细胞代谢及分子生物学功能方面的作 用已经被部分证实，并且，作为一种肿瘤相关基 因，ARL4C与肺癌、结直肠癌、胃癌、睾丸癌、黑 色素瘤、原发性人胶质母细胞瘤、卵巢癌发生发展 也具有相关性。笔者研究曾经证实了 ARL4C作为一 种新型 Wnt信号靶分子调控了肾透明细胞癌的上皮 间质转化，同时导致了肿瘤细胞的增殖、侵袭和迁 移能力的改变。进一步研究 ARL4C与不同肿瘤的发 生、发展的关系及其深入的作用机制，可能为肿瘤 的基因诊断和治疗提供新的预后标记物和治疗靶点。

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