SALL4的促癌功能及治疗意义

Pro-oncogenic Function and Therapeutic Significance of SALL4

婆罗双树样基因4(spalt-like transcription factor 4,SALL4)是2002年发现的SALL转录因子家族新成员,在维持胚胎干细胞(embryonic stem cells,ESCs)自我更新和多能性方面起着至关重要的作用。SALL4在胚胎干细胞和生殖细胞中特异表达,而在大多数成体细胞中表达下调或沉默。然而,近年来的研究表明,SALL4可以在白血病、乳腺癌、胃癌、卵巢癌、肝癌、肺癌、黑色素瘤等多种肿瘤中表达,显示出癌胚抗原特性,且SALL4表达水平与肿瘤进展及患者的不良预后和生存期直接相关。SALL4在肿瘤中的表达是由多种细胞因子介导的,并作为转录因子调控下游基因表达和信号通路,进而促进肿瘤的发生、转移、代谢和耐药等。靶向抑制SALL4的表达或生物学功能已经显示出显著的抗肿瘤效果。由于SALL4在肿瘤组织中的高表达和促进肿瘤发展的特性,它被认为是新的肿瘤标志物和潜在的治疗靶点。简要概述了SALL4蛋白的结构和功能,探讨了其激活表达的分子机制,并着重介绍了SALL4在肿瘤发生和发展中的作用机制、其在诊断上的价值以及靶向治疗的潜在意义。希望能够为肿瘤的临床治疗提供有益的参考数据。

Spalt-like gene 4(SALL4),a new member of the SALL transcription factor family discovered in 2002,plays a crucial role in maintaining self-renewal and pluripotent embryonic stem cells(ESCs).SALL4 is specifically expressed in embryonic stem cells and germ cells,but is down-regulated or silenced in most adult cells.However,recent studies have shown that SALL4 is re-expressed in leukemia,breast cancer,stomach cancer,ovarian cancer,liver cancer,lung cancer,melanoma and other tumors,showing its characteristics of proto-oncogene,and the expression level of SALL4 is directly correlated to tumor progression,poor prognosis and survival of patients.The re-expression of SALL4 is mediated by a variety of cytokines,and acts as a transcription factor to regulate expressions of downstream gene and signaling pathways to promote tumor occurrence,metastasis,metabolism and drug resistance.Targeted inhibition of SALL4 expression and biological function shows obvious antitumor effect.SALL4 has become a new tumor marker and potential therapeutic target due to its properties of re-expression in tumor tissues and promoting tumor occurrence and development.The article summerized the structure and function of SALL4 protein,and its molecular mechanism of activation expression.This article focused on the mechanism and diagnostic value of SALL4 molecule in the development of tumor and the significance of targeted therapy,which was expected to provide reference data for cancer therapy.