Abstract
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.
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Acknowledgements
This work was supported by the Major Research Plan of the National Natural Science Foundation of China (Grant no. 91129718), the National Natural Science Foundation of China (Grant no. 81071421), the Natural Science Foundation of the Jiangsu Province (Grant no. BK2012709), Jiangsu Province’s Project of Scientific and Technological Innovation and Achievements Transformation (Grant no. BL2012055), Jiangsu Province’s Outstanding Medical Academic Leader and Sci-tech Innovation Team Program (Grant no. LJ201117), Jiangsu Province Doctoral Innovation Fund (Grant no. CXLX12_0678) and Doctoral Program Foundation of State Education Ministry (Grant no. 20113227110011).
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Zhang, L., Xu, Z., Xu, X. et al. SALL4, a novel marker for human gastric carcinogenesis and metastasis. Oncogene 33, 5491–5500 (2014). https://doi.org/10.1038/onc.2013.495
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DOI: https://doi.org/10.1038/onc.2013.495
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