STAT1 acts as a tumor promoter for leukemia development
STAT1 acts as a tumor promoter for leukemia development
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DOI：
10.1016/j.ccr.2006.05.025
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发表时间：
2006-07-01
期刊：
影响因子：
50.3
通讯作者：
Sexl, Veronika
中科院分区：
文献类型：
--
作者：
Kovacic, Boris;Stoiber, Dagmar;Sexl, Veronika
肿瘤抑制基因STAT1被认为是监测发展中肿瘤的关键调节因子。在这里，我们描述了STAT1在白血病中一个意想不到的促肿瘤作用。STAT1(-/-)小鼠可以部分避免白血病的发生，而在RAG2(-/-)和免疫活性小鼠中，STAT1(-/-)肿瘤细胞诱导白血病的潜伏期延长。STAT1(-/-)肿瘤细胞的低MHC-I类蛋白水平能够有效地裂解NK细胞，并解释了肿瘤清除的增强。值得注意的是，STAT1(-/-)肿瘤细胞在白血病进展过程中MHC-I类表达增加。这些发现将STAT1定义为白血病发生中的肿瘤促进剂。此外，我们将MHC-I类分子的表达上调描述为一种允许血液系统恶性肿瘤逃避免疫监视的一般机制。
The tumor suppressor STAT1 is considered a key regulator of the surveillance of developing tumors. Here, we describe an unexpected tumor-promoting role for STAT1 in leukemia. STAT1(-/-) mice are partially protected from leukemia development, and STAT1(-/-) tumor cells induce leukemia in RAG2(-/-) and immunocompetent mice with increased latency. The low MHC class I protein levels of STAT1(-/-) tumor cells enable efficient NK cell lysis and account for the enhanced tumor clearance. Strikingly, STAT1(-/-) tumor cells acquire increased MHC class I expression upon leukemia progression. These findings define STAT1 as a tumor promoter in leukemia development. Furthermore, we describe the upregulation of MHC class I expression as a general mechanism that allows for the escape of hematopoietic malignancies from immune surveillance.