SALL2 represses cyclins D1 and E1 expression and restrains G1/S cell cycle transition and cancer-related phenotypes.
SALL2 represses cyclins D1 and E1 expression and restrains G1/S cell cycle transition and cancer-related phenotypes.
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DOI：
10.1002/1878-0261.12308
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发表时间：
2018-06
影响因子：
6.6
通讯作者：
Pincheira R
中科院分区：
文献类型：
--
作者：
E Hermosilla V;Salgado G;Riffo E;Escobar D;Hepp MI;Farkas C;Galindo M;Morín V;García-Robles MA;Castro AF;Pincheira R
SALL2是一个功能较差的转录因子，属于参与发育的Spalt样家族。SALL2上的突变与眼部缺损和癌症有关。在癌症中，SALL2被解除调控，并被认为是卵巢癌的肿瘤抑制因子。SALL2与干细胞分化、细胞死亡、增殖和静止有关。然而，SALL2与癌症相关的潜在作用机制在很大程度上仍不清楚。在这里，我们利用来自SALL2−/−小鼠的小鼠胚胎成纤维细胞(MEF)研究了SALL2在细胞增殖中的作用。与SALL2+/+−/−相比，SALL2 MEF在G1期和S期表现出更强的细胞增殖能力和更快的分裂后进程。相应地，SALL2−/−MEF表现出较高的细胞周期蛋白D1mRNA和蛋白水平。染色质免疫沉淀和启动子报告分析表明，SALL2结合并抑制CCND1和CCNE1启动子，从而确定了SALL2控制细胞周期的新机制。此外，对SALL2+/+和SALL2−/−小鼠组织的分析证实，SALL2和G1-S细胞周期蛋白的表达呈负相关。与SALL2的抗增殖功能一致，永生化的SALL2−/−MEF表现出更快的生长速度、病灶形成和非锚定生长，证实了SALL2的肿瘤抑制特性。最后，癌症数据分析显示，在几种癌症中，SALL2和G1-S细胞周期蛋白的表达水平呈负相关。综上所述，我们的结果表明，SALL2是细胞增殖的负调控因子，其作用部分是通过抑制G1-S细胞周期蛋白的表达来实现的。我们的结果对于理解SALL2在生理和病理条件下的作用和意义具有重要意义。
SALL2 is a poorly characterized transcription factor that belongs to the Spalt‐like family involved in development. Mutations on SALL2 have been associated with ocular coloboma and cancer. In cancers, SALL2 is deregulated and is proposed as a tumor suppressor in ovarian cancer. SALL2 has been implicated in stemness, cell death, proliferation, and quiescence. However, mechanisms underlying roles of SALL2 related to cancer remain largely unknown. Here, we investigated the role of SALL2 in cell proliferation using mouse embryo fibroblasts (MEFs) derived from Sall2 −/− mice. Compared to Sall2 +/+ MEFs, Sall2 −/− MEFs exhibit enhanced cell proliferation and faster postmitotic progression through G1 and S phases. Accordingly, Sall2 −/− MEFs exhibit higher mRNA and protein levels of cyclins D1 and E1. Chromatin immunoprecipitation and promoter reporter assays showed that SALL2 binds and represses CCND1 and CCNE1 promoters, identifying a novel mechanism by which SALL2 may control cell cycle. In addition, the analysis of tissues from Sall2 +/+ and Sall2 −/− mice confirmed the inverse correlation between expression of SALL2 and G1‐S cyclins. Consistent with an antiproliferative function of SALL2, immortalized Sall2 −/− MEFs showed enhanced growth rate, foci formation, and anchorage‐independent growth, confirming tumor suppressor properties for SALL2. Finally, cancer data analyses show negative correlations between SALL2 and G1‐S cyclins’ mRNA levels in several cancers. Altogether, our results demonstrated that SALL2 is a negative regulator of cell proliferation, an effect mediated in part by repression of G1‐S cyclins’ expression. Our results have implications for the understanding and significance of SALL2 role under physiological and pathological conditions.
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影响因子：
5.6
作者：
Henriquez, Berta;Hepp, Matias;Merino, Paola;Sepulveda, Hugo;Van Wijnen, Andre J.;Lian, Jane B.;Stein, Gary S.;Stein, Janet L.;Montecino, Martin
通讯作者：
Montecino, Martin
DOI：
10.1016/j.bbagrm.2011.02.002
发表时间：
2011-04
影响因子：
4.7
作者：
Gu, Hongcang;Li, Dawei;Sung, Chang K.;Yim, Hyungshin;Troke, Philip;Benjamin, Thomas
通讯作者：
Benjamin, Thomas
影响因子：
4.8
作者：
Janbandhu, Vaibhao C.;Singh, Anup K.;Kumar, Vijay
通讯作者：
Kumar, Vijay
DOI：
10.4137/bic.s38394
发表时间：
2016
期刊：
Biomarkers in cancer
影响因子：
--
作者：
Inoue K;Fry EA
通讯作者：
Fry EA
DOI：
10.1186/bcr3441
发表时间：
2013-06-20
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dai M;Al-Odaini AA;Fils-Aimé N;Villatoro MA;Guo J;Arakelian A;Rabbani SA;Ali S;Lebrun JJ
通讯作者：
Lebrun JJ