Ludwig Boltzmann Institute for Cancer Research, A-1090 Vienna, Austria.
Gastroenterology. 2010 Mar;138(3):1003-11.e1-5. doi: 10.1053/j.gastro.2009.11.049. Epub 2009 Dec 4.
The transcription factor signal transducer and activator of transcription 3 (Stat3) has been considered to promote progression and metastasis of intestinal cancers.
We investigated the role of Stat3 in intestinal tumors using mice with conditional ablation of Stat3 in intestinal epithelial cells (Stat3(DeltaIEC)).
In the Apc(Min) mouse model of intestinal cancer, genetic ablation of Stat3 reduced the multiplicity of early adenomas. However, loss of Stat3 promoted tumor progression at later stages, leading to formation of invasive carcinomas, which significantly shortened the lifespan of Stat3(DeltaIEC)Apc(Min/+) mice. Interestingly, loss of Stat3 in tumors of Apc(Min/+) mice had no significant impact on cell survival and angiogenesis, but promoted cell proliferation. A genome-wide expression analysis of Stat3-deficient tumors suggested that Stat3 might negatively regulate intestinal cancer progression via the cell adhesion molecule CEACAM1.
Our data suggest that Stat3 impairs invasiveness of intestinal tumors. Therefore, therapeutic targeting of the Stat3 signaling pathway in intestinal cancer should be evaluated for adverse effects on tumor progression.
转录因子信号转导子和转录激活子 3（Stat3）被认为可促进肠癌细胞的进展和转移。
我们使用条件性敲除肠上皮细胞中 Stat3 的小鼠（Stat3（ΔIEC））来研究 Stat3 在肠道肿瘤中的作用。
在肠腺癌 Apc（Min）小鼠模型中，Stat3 的遗传缺失减少了早期腺瘤的数量。然而，Stat3 的缺失促进了晚期肿瘤的进展，导致侵袭性癌的形成，这显著缩短了 Stat3（ΔIEC）Apc（Min/+）小鼠的寿命。有趣的是，Stat3 在 Apc（Min/+）小鼠肿瘤中的缺失对细胞存活和血管生成没有显著影响，但促进了细胞增殖。对 Stat3 缺失肿瘤的全基因组表达分析表明，Stat3 可能通过细胞黏附分子 CEACAM1 负调控肠道癌症的进展。
我们的数据表明 Stat3 损害了肠道肿瘤的侵袭性。因此，应评估针对肠道癌症中 Stat3 信号通路的治疗性靶向作用对肿瘤进展的不良影响。
