SALL4 is a new target in endometrial cancer.
SALL4 is a new target in endometrial cancer.
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作者：
侵袭性癌症和胚胎干 (ES) 细胞具有共同的基因表达特征。识别该 ES 特征中导致癌症侵袭性的关键因素/途径可以带来潜在的治愈方法。在这项研究中，我们发现SALL4（一种参与维持ES细胞自我更新的基因）在47.7%的原发性人类子宫内膜癌样本中异常表达。它在正常或增生的子宫内膜中不表达。更重要的是，SALL4 表达与较差的患者生存率和侵袭性特征（例如子宫内膜癌的转移）呈正相关。进一步的功能研究表明，SALL4 的缺失会抑制子宫内膜癌细胞的体外生长和体内致瘤性，因为细胞增殖受到抑制，细胞凋亡增加。此外，SALL4的下调显着阻碍子宫内膜癌细胞的体外迁移和侵袭特性及其体内转移潜力。此外，控制SALL4表达可以影响子宫内膜癌细胞对卡铂的药物敏感性。此外，我们发现 SALL4 特异性结合子宫内膜癌细胞中的 c-Myc 启动子区域。虽然SALL4的下调导致c-Myc在蛋白质和mRNA水平上的表达降低，但异位SALL4过表达导致c-Myc蛋白和mRNA表达增加，表明c-Myc是子宫内膜肿瘤发生中SALL4下游靶标之一。总之，我们首次证明 SALL4 在侵袭性子宫内膜癌的转移和耐药性中发挥功能作用。由于其在癌细胞中的功能作用以及在正常组织中的缺失，SALL4 是高风险子宫内膜癌患者群体的潜在新治疗靶点。
Aggressive cancers and embryonic stem (ES) cells share a common gene expression signature. Identifying the key factors/pathway(s) within this ES signature responsible for the aggressiveness of cancers can lead to a potential cure. In this study, we find that SALL4, a gene involved in the maintenance of ES cell self-renewal, is aberrantly expressed in 47.7% of primary human endometrial cancer samples. It is not expressed in normal or hyperplastic endometrial. More importantly, SALL4 expression is positively correlated with worse patient survival and aggressive features such as metastasis in endometrial carcinoma. Further functional studies have shown that loss of SALL4 inhibits endometrial cancer cell growth in vitro and tumorigenicity in vivo, as a result of inhibition of cell proliferation and increased apoptosis. In addition, down-regulation of SALL4 significantly impedes the migration and invasion properties of endometrial cancer cells in vitro and their metastatic potential in vivo. Furthermore, manipulation of SALL4 expression can affect drug sensitivity of endometrial cancer cells to carboplatin. Moreover, we show that SALL4 specifically binds to the c-Myc promoter region in endometrial cancer cells. While down-regulation of SALL4 leads to a decreased expression of c-Myc at both protein and mRNA levels, ectopic SALL4 overexpression causes increased c-Myc protein and mRNA expression, indicating that c-Myc is one of the SALL4 downstream targets in endometrial tumorigenesis. In summary, we are the first to demonstrate that SALL4 plays functional role(s) in metastasis and drug resistance in aggressive endometrial cancer. As a consequence of its functional roles in cancer cell and absence in normal tissue, SALL4 is a potential novel therapeutic target for the high risk endometrial cancer patient population.
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影响因子：
3.7
作者：
Jeong HW;Cui W;Yang Y;Lu J;He J;Li A;Song D;Guo Y;Liu BH;Chai L
通讯作者：
Chai L
DOI：
10.1073/pnas.0407772101
发表时间：
2005-01-04
影响因子：
11.1
作者：
Renaud, EJ;MacLaughlin, DT;Donahoe, PK
通讯作者：
Donahoe, PK
影响因子：
20.3
作者：
Ma, Yupo;Cui, Wei;Chai, Li
通讯作者：
Chai, Li
影响因子：
2.3
作者：
Knapp, DC;Mata, JE;Iversen, PL
通讯作者：
Iversen, PL
影响因子：
64.8
作者：
LITTLE, CD;NAU, MM;MINNA, JD
通讯作者：
MINNA, JD