CUX1及其分子调控机制在人类恶性肿瘤中的研究进展

Advances in the study of CUX1 and its molecular regulatory mechanisms in human malignant tumors

同源框CUT样蛋白1(CUX1),又称CDP(CCAAT位移蛋白),CUT或CUTL1,是DNA结合蛋白同源域家族的成员。CUX1基因在转录和翻译过程中形成不同长度的蛋白亚型,包括P200、P110和P75。除髓系白血病外,CUX1蛋白被发现在乳腺癌、肺癌、胰腺癌、胶质瘤、胰腺神经内分泌肿瘤等多种癌组织中过表达,在癌旁组织中不表达或低表达,且表达量与肿瘤恶性程度和病人预后相关。因此,CUX1可作为多种恶性肿瘤诊断的新型分子标志物及治疗靶点。在肿瘤中的长期研究中逐渐明晰CUX1的作用机制,解释其癌基因和抑癌基因的矛盾。在机制研究中发现,全长CUX1蛋白可以促进DNA碱基修复,与肿瘤耐药性相关;CUX1短亚型可以通过介导PI3K/AKT,Wnt/β-catenin,TGF-β等信号通路调控肿瘤的增殖、迁移和侵袭过程。本文重点介绍CUX1与肿瘤的相关性及其调控机制的研究进展。

Cut like hemeobox 1 protein (CUX1), also known as CDP、CUT or CUTL1, is a member of homeodomain DNAbinding protein family. In the process of transcription and translation, CUX1 gene can produce different protein isoforms with different lengths, including p200, P110 and p75. The loss of CUX1 plays a positive role in Myeloid Leukemia as reported. On the contrary, CUX1 overexpresses is found in a lot kinds of cancers, such as mammary cancer, lung cancer, pancreatic cancer, glioma and pancreatic neuroendocrine tumor, and its expression level is connected with patients prognosis. So, CUX1 can act as a potential biologic marker and therapeutic target for diagnosis and prognosis of tumors. The paradox role of CUX1 in cancers can be explained with researches after a long time. In the fundamental studies, P200 as an unabridged protein isoform can stimulate DNA base repairing, which is associated with the pharmaceutic resistance of cancer;and the short isoforms of CUX1 can regulate the proliferation, migration and invasion through regulating some signal pathways, such as PI3k/AKT、 Wnt/β-catenin and TGF-β pathways. This review aims to introduce the research progress about correlation analysis and regulatory mechanism of CUX1 in different tumors.