SALL4, a novel marker for human gastric carcinogenesis and metastasis
SALL4, a novel marker for human gastric carcinogenesis and metastasis
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SALL4，人类胃癌发生和转移的新标志物
DOI：
10.1038/onc.2013.495
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发表时间：
2014-11-27
期刊：
影响因子：
8
通讯作者：
Xu, W.
中科院分区：
文献类型：
--
作者：
Zhang, L.;Xu, Z.;Xu, W.
SALL 4是一种锌指转录因子，具有胚胎干细胞自我更新和多能性的功能，被认为与肿瘤发生有关。然而，SALL 4在人类胃癌中的作用在很大程度上仍然未知。本研究证实SALL 4在胃癌组织中的表达在mRNA和蛋白水平上均存在异常，且SALL 4水平与胃癌淋巴结转移密切相关。SALL 4的表达增强了人胃癌细胞的增殖和迁移，而通过siRNA敲低SALL 4则导致相反的效果。此外，SALL 4过表达促进了胃移植瘤的生长和转移。SALL 4过表达可诱导胃癌细胞发生上皮间质转化（EMT），Twist 1、N-cadherin表达增加，E-cadherin表达减少。此外，SALL 4通过Bmi-1和Lin 28 B诱导胃癌细胞获得干细胞。综上所述，我们的研究结果表明，SALL 4通过调节EMT和细胞干细胞性在胃癌中具有致癌作用，表明SALL 4作为人类胃癌诊断和治疗的新靶点。
SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal and pluripotency, has been suggested to be involved in tumorigenesis. The role of SALL4 in human gastric cancer, however, remains largely unknown. In this study, we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein levels in human gastric cancer tissues, and SALL4 level was highly correlated with lymph node metastasis. Enforced expression of SALL4 enhanced the proliferation and migration of human gastric cancer cells, whereas knockdown of SALL4 by siRNA led to the opposite effects. In addition, SALL4 overexpression promoted the growth and metastasis of gastric xenograft tumor in vivo. SALL4 overexpression induced epithelial–mesenchymal transition (EMT) in gastric cancer cells, with increased expression of Twist1, N-cadherin and decreased expression of E-cadherin. Moreover, SALL4 promoted the acquirement of stemness in gastric cancer cells through the induction of Bmi-1 and Lin28B. Taken together, our findings indicate that SALL4 has oncogenic roles in gastric cancer through the modulation of EMT and cell stemness, suggesting SALL4 as a novel target for human gastric cancer diagnosis and therapy.