Atypical chemokine receptor 3 induces colorectal tumorigenesis in vivo acting on the NOLC1 with Fibrillarin dependent rRNA biogenesis
Atypical chemokine receptor 3 induces colorectal tumorigenesis in vivo acting on the NOLC1 with Fibrillarin dependent rRNA biogenesis
复制标题
非典型趋化因子受体 3 通过纤维蛋白依赖的 rRNA 生物发生作用于 NOLC1 诱导体内结直肠肿瘤发生
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发表时间：
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影响因子：
8.2
通讯作者：
Shuxiang Cui
中科院分区：
文献类型：
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作者：
Yang Juan;Rongrong Miao;Yanan Li;Ting Pan;Shuhua Wu;Xianjun Qu;Shuxiang Cui
Atypical chemokine receptor 3 (ACKR3) has emerged as a key player in several biologic processes. Its atypical “intercepting receptor” properties have established ACKR3 as the major regulator in the pathophysiological processes in many diseases. Here, we revealed a new mechanism of ACKR3 activation in promoting colorectal tumorigenesis. In human colonic cancer tissues, ACKR3 was activated and high levels of ACKR3 predicated the increased severity of cancer. In Villin-ACKR3 transgenic mice, AOM/DSS induced more severity of colorectal tumorigenesis than their WT littermates. Cancer cells of Villin-ACKR3 transgenic mice were characterized by the nuclear β-arrestin-1-activated perturbation of rRNA biogenesis. Activation of ACKR3 induced nuclear translocation of β-arrestin-1 (β-arr1), leading to an interaction of β-arr1 with nucleolar and coiled-body phosphoprotein 1 (NOLC1). As the phosphorylated protein, NOLC1 further interacted with Fibrillarin, a conserved nucleolar methyltransferase responsible for ribosomal RNA methylation in nucleolus, increasing the methylation in Histone H2A, and finally promoting rRNA transcription of ribosome biogenesis. Conclusion: ACKR3 promotes colorectal tumorigenesis through the perturbation of rRNA biogenesis by β-arr1-induced an interaction of NOLC1 with Fibrillarin.
