Special AT-rich sequence-binding protein 2 acts as a negative regulator of stemness in colorectal cancer cells.
Special AT-rich sequence-binding protein 2 acts as a negative regulator of stemness in colorectal cancer cells.
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富含 AT 的特殊序列结合蛋白 2 作为结直肠癌细胞干性的负调节因子
DOI：
10.3748/wjg.v22.i38.8528
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发表时间：
2016-10-14
影响因子：
4.3
通讯作者：
Li JM
中科院分区：
文献类型：
--
作者：
Li Y;Liu YH;Hu YY;Chen L;Li JM
目的探讨特异性AT富含序列结合蛋白2(SATB2)影响结直肠癌转移的机制。方法采用细胞生长实验、集落形成实验、细胞黏附实验和细胞迁移实验检测SATB2获得或缺失对结直肠癌细胞生物学特性的影响。球体形成实验检测CRC细胞的自我更新能力。用实时定量聚合酶链式反应检测SATB2表达上调或下调的大肠癌细胞中干细胞标志物的mRNA表达。用染色质免疫沉淀法(ChIP)验证SATB2在干细胞标记物基因组序列上的结合位点。对TCGA数据库和我们的临床样本进行分析，找出SATB2与一些关键干细胞标记物的相关性。结果SATB2基因下调导致SW480和DLD-1细胞发生侵袭性表型，表现为迁移和侵袭能力增强。SATB2过表达抑制了SW480和SW620细胞的迁移和侵袭能力。用序贯球体形成实验检测大肠癌细胞的自我更新能力，发现SATB2表达下调后，SW480和DLD-1细胞中次级球体形成较多，而原发球体形成较少。在SATB2基因敲除的细胞中，CD133、CD44、AXIN2、MEIS2和NANOG等大多数干细胞标志物增加，在SATB2过表达的细胞中减少。芯片分析表明，SATB2与CD133、CD44、MEIS2和AXIN2基因的调控元件结合。利用TCGA数据库和我们的临床标本，我们发现SATB2与结直肠癌患者临床组织中的一些关键干细胞标记物CD44和CD24相关。结论SATB2可直接与多个干细胞标志物基因座上的调控元件结合，通过负性调节结直肠癌细胞的干性，从而抑制结直肠癌的进展。
AIM To find the mechanisms by which special AT-rich sequence-binding protein 2 (SATB2) influences colorectal cancer (CRC) metastasis. METHODS Cell growth assay, colony-forming assay, cell adhesion assay and cell migration assay were used to evaluate the biological characteristics of CRC cells with gain or loss of SATB2. Sphere formation assay was used to detect the self-renewal ability of CRC cells. The mRNA expression of stem cell markers in CRC cells with upregulated or downregulated SATB2 expression was detected by quantitative real-time polymerase chain reaction. Chromatin immunoprecipitation (ChIP) was used to verify the binding loci of SATB2 on genomic sequences of stem cell markers. The Cancer Genome Atlas (TCGA) database and our clinical samples were analyzed to find the correlation between SATB2 and some key stem cell markers. RESULTS Downregulation of SATB2 led to an aggressive phenotype in SW480 and DLD-1 cells, which was characterized by increased migration and invasion abilities. Overexpression of SATB2 suppressed the migration and invasion abilities in SW480 and SW620 cells. Using sequential sphere formation assay to detect the self-renewal abilities of CRC cells, we found more secondary sphere formation but not primary sphere formation in SW480 and DLD-1 cells after SATB2 expression was knocked down. Moreover, most markers for stem cells such as CD133, CD44, AXIN2, MEIS2 and NANOG were increased in cells with SATB2 knockdown and decreased in cells with SATB2 overexpression. ChIP assay showed that SATB2 bound to regulatory elements of CD133, CD44, MEIS2 and AXIN2 genes. Using TCGA database and our clinical samples, we found that SATB2 was correlated with some key stem cell markers including CD44 and CD24 in clinical tissues of CRC patients. CONCLUSION SATB2 can directly bind to the regulatory elements in the genetic loci of several stem cell markers and consequently inhibit the progression of CRC by negatively regulating stemness of CRC cells.
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影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
SATB2表达下调与结直肠癌转移和不良预后相关
影响因子：
7.3
作者：
Wang, Shuang;Zhou, Jun;Li, Jian-Ming
通讯作者：
Li, Jian-Ming
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
DOI：
10.1186/bcr1855
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Wright MH;Calcagno AM;Salcido CD;Carlson MD;Ambudkar SV;Varticovski L
通讯作者：
Varticovski L