Rho 激酶调节携带致癌形式 KIT、FLT3 和 BCR-ABL 的细胞的存活和转化。
Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL.
机构信息
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA.
出版信息
Cancer Cell. 2011 Sep 13;20(3):357-69. doi: 10.1016/j.ccr.2011.07.016.
Abstract
We show constitutive activation of Rho kinase (ROCK) in cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL, which is dependent on PI3K and Rho GTPase. Genetic or pharmacologic inhibition of ROCK in oncogene-bearing cells impaired their growth as well as the growth of acute myeloid leukemia patient-derived blasts and prolonged the life span of mice bearing myeloproliferative disease. Downstream from ROCK, rapid dephosphorylation or loss of expression of myosin light chain resulted in enhanced apoptosis, reduced growth, and loss of actin polymerization in oncogene-bearing cells leading to significantly prolonged life span of leukemic mice. In summary we describe a pathway involving PI3K/Rho/ROCK/MLC that may contribute to myeloproliferative disease and/or acute myeloid leukemia in humans.
摘要
我们发现，携带致癌形式的 KIT、FLT3 和 BCR-ABL 的细胞中 Rho 激酶（ROCK）持续激活，这依赖于 PI3K 和 Rho GTPase。在携带致癌基因的细胞中，ROCK 的遗传或药理学抑制会损害它们的生长以及急性髓系白血病患者来源的白血病细胞的生长，并延长患有骨髓增生性疾病的小鼠的寿命。ROCK 的下游，肌球蛋白轻链的快速去磷酸化或表达缺失导致凋亡增加、生长减少和肌动蛋白聚合丧失，从而导致白血病小鼠的寿命显著延长。总之，我们描述了一条涉及 PI3K/Rho/ROCK/MLC 的通路，该通路可能导致人类骨髓增生性疾病和/或急性髓系白血病。
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