期刊
ONCOGENE
卷 31, 期 35, 页码 3913-3923出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.560
关键词
DLC1; MKL1; MKL2; MRTF; Rho; SRF
资金
- German Research Foundation (DFG) [MU 2737/2-1]
- National Cancer Institute [CA050329]
Deleted in Liver Cancer 1 (DLC1) is a tumor suppressor whose allele is lost in 50% of liver, breast, lung and 70% of colon cancers. Here, we show that the transcriptional coactivators Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are constitutively localized to the nucleus in hepatocellular and mammary carcinoma cells that lack DLC1. Moreover, DLC1 loss and MKL1 nuclear localization correlate in primary human hepatocellular carcinoma. Nuclear accumulation of MKL1 in DLC1 deficient cancer cells is accomplished by activation of the RhoA/actin signaling pathway and concomitant impairment of MKL1 phosphorylation, which results in constitutive activation of MKL1/2 target genes. We provide evidence that MKL1/2 mediates cancerous transformation in DLC1-deficient hepatocellular and mammary carcinoma cells. Depletion of MKL1/2 suppresses cell migration, cell proliferation and anchorage-independent cell growth induced by DLC1 loss. Oncogene (2012) 31, 3913-3923; doi:10.1038/onc.2011.560; published online 5 December 2011
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据