Abstract
Sal-like protein 4 (SALL4) has been proved to play a pivotal role in the development and progression of various cancers. Previous studies showed that SALL4 was highly expressed in human choriocarcinoma tissues. However, the role of SALL4 in the biological behavior of human choriocarcinoma cells remains largely unknown. In this study, we first elucidated that SALL4 was highly expressed in human choriocarcinoma cell lineJEG-3 and JAR. Sal-like protein 4 knockdown by small interfering RNA (siRNA) decreased c-Myc expression, whereas SALL4 overexpression by transfection of human pLenti-SALL4 construct promoted c-Myc expression. Further data showed that SALL4 overexpression improved cell proliferation of JEG-3 cells, which can be abrogated by c-Myc siRNA. Moreover, our data showed that SALL4 interact with β-catenin and SALL4 overexpression promoted the loca- lization of β-catenin in the nucleus and β-catenin siRNA abrogated SALL4-induced c-Myc expression in JEG-3 cells. These data indicate that aberrantly expressed SALL4 in human choriocarcinoma cells may promote cell proliferation via β-catenin/c-Myc pathway, indicating that SALL4 may be potential treatment targets of human choriocarcinoma.
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References
Yang J, Chai L, Fowles TC, et al. Genome-wide analysis reveals SALL4 to be a major regulator of pluripotency in murine embryonic stem cells. Proc Natl Acad Sci USA. 2008;105(50):19756–19761.
Zhang J, Tam WL, Tong GQ, et al. SALL4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol. 2006;8(10):1114–1123.
Gao C, Dimitrov T, Yong KJ, et al. Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex. Blood. 2013;121(8):1413–1421.
Oikawa T, Kamiya A, Zeniya M, et al. Sal-like protein 4 (SALL4), a stem cell biomarker in liver cancers. Hepatology. 2013;57(4):1469–1483.
Cheng J, Deng R, Wu C, et al. Shi L Inhibition of SALL4 suppresses carcinogenesis of colorectal cancer via regulating Gli1 expression. Int J Clin Exp Pathol. 2015;8(9):10092–10101.
Kobayashi D, Kuribayshi K, Tanaka M, Watanabe N. SALL4 is essential for cancer cell proliferation and is overexpressed at early clinical stages in breast cancer. Int J Oncol. 2011;38(4):933–939.
Li A, Jiao Y, Yong KJ, et al. SALL4 is a new target in endometrial cancer. Oncogene. 2015;34(1):63–72.
Kobayashi D, Kuribayashi K, Tanaka M, Watanabe N. Overexpression of SALL4 in lung cancer and its importance in cell proliferation. Oncol Rep. 2011;26(4):965–970.
Zhang L, Xu Z, Xu X, et al. SALL4, a novel marker for human gastric carcinogenesis and metastasis. Oncogene. 2014;33(48): 5491–5500.
Zhang X, Yuan X, Zhu W, Qian H, Xu W. SALL4: an emerging cancer biomarker and target. Cancer Lett. 2015;357(1):55–62.
Elling U, Klasen C, Eisenberger T, Anlag K, Treier M. Murine inner cell mass-derived lineages depend on SALL4 function. Proc Natl Acad Sci USA. 2006;103(44):16319–16324.
Yuri S, Fujimura S, Nimura K, et al. SALL4 is essential for stabilization, but not for pluripotency, of embryonic stem cells by repressing aberrant trophectoderm gene expression. Stem Cells. 2009;27(4):796–805.
Stichelbout M, Devisme L, Franquet-Ansart H, et al. SALL4 expression in gestational trophoblastic tumors: a useful tool to distinguish choriocarcinoma from placental site trophoblastic tumor and epithelioid trophoblastic tumor. Hum Pathol. 2016;54:121–126.
Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127(3):469–480.
Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.
Krivega M, Essahib W, Van de Velde H. WNT3 and membraneassociated β-catenin regulate trophectoderm lineage differentiation in human blastocysts. Mol Hum Reprod. 2015;21(9): 711–722.
Matsuura K, Jigami T, Taniue K, et al. Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway. Nat Commun. 2011;2:548.
Ma Y, Cui W, Yang J, et al. SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice. Blood. 2006;108(8): 2726–2735.
Shuai X, Zhou D, Shen T, et al. Overexpression of the novel oncogene SALL4 and activation of the Wnt/beta-catenin pathway in myelodysplastic syndromes. Cancer Genet Cytogenet. 2009;194(2):119–124.
He J, Zhou M, Chen X, et al. Inhibition of SALL4 reduces tumorigenicity involving epithelial-mesenchymal transition via Wnt/β-catenin pathway in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2016;35(1):98.
Zhao HB, Tang CL, Hou YL, et al. CXCL12/CXCR4 axis triggers the activation of EGF receptor and ERK signaling pathway in CsA-induced proliferation of human trophoblast cells. PLoS One. 2012;7(7):e38375.
Liu L, Zhang J, Yang X, Fang C, Xu H, Xi X. SALL4 as an epithelial-mesenchymal transition and drug resistance inducer through the regulation of c-Myc in endometrial cancer. PLoS One. 2015;10(9):e0138515.
Betteridge KJ. Equine embryology: an inventory of unanswered questions. Theriogenology. 2007;68(suppl 1):S9–S21
Robson SC, Simpson H, Ball E, Lyall F, Bulmer JN. Punch biopsy of the human placental bed. Am J Obstet Gynecol. 2002;187(5): 1349–1355.
Gauster M, Moser G, Orendi K, Huppertz B. Factors involved in regulating trophoblast fusion: potential role in the development of preeclampsia. Placenta. 2009;30(suppl A):S49–S54.
Goodwin AM, Kitajewski J, D’Amore PA. Wnt1 and Wnt5a affect endothelial proliferation and capillary length; Wnt2 does not. Growth Factors. 2007;25(1):25–32.
Lee JG, Heur M. WNT10B Enhances proliferation through betacatenin and RAC1 GTPase in human corneal endothelial cells. Biol Chem. 2015;290(44):26752–26764.
MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1): 9–26.
Morin PJ, Sparks AB, Korinek V, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275(5307):1787–1790.
Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14(15): 1837–1851.
Al-Harthi L. Wnt/beta-catenin and its diverse physiological cell signaling pathways in neurodegenerative and neuropsychiatric disorders. J. Neuroimmune Pharmacol. 2012;7(4):725–730.
Wang J, Fang X, Liang W. Pegylated phospholipid micelles induce endoplasmic reticulum-dependent apoptosis of cancer cells but not normal cells. ACS Nano. 2012;6(6):5018–5030.
Bregoli L, Chiarini F, Gambarelli A, et al. Toxicity of antimony trioxide nanoparticles on human hematopoietic progenitor cells and comparison to cell lines. Toxicology. 2009;262(2):121–129.
Liu X, Krawczyk E, Suprynowicz FA, et al. Conditional reprogramming and long-term expansion of normal and tumor cells from human biospecimens. Nat Protoc. 2017;12(2):439–451.
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Zhao, H., Wu, L., Wu, J. et al. Aberrantly Expressed SALL4 Promotes Cell Proliferation via β-Catenin/c-Myc Pathway in Human Choriocarcinoma Cells. Reprod. Sci. 25, 435–442 (2018). https://doi.org/10.1177/1933719117715130
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DOI: https://doi.org/10.1177/1933719117715130