Dyrk1B overexpression is associated with breast cancer growth and a poor prognosis
Dyrk1B overexpression is associated with breast cancer growth and a poor prognosis
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Dyrk1B 过度表达与乳腺癌生长和不良预后相关
DOI：
10.1016/j.humpath.2017.02.033
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发表时间：
2017-08-01
期刊：
影响因子：
3.3
通讯作者：
Cheng, Chun
中科院分区：
文献类型：
--
作者：
Chen, Yingying;Wang, Shuo;Cheng, Chun
Dyrk 1B，也称为minibrain-related kinase（Mirk），是双特异性酪氨酸磷酸化调节激酶（Dyrk）/minibrain双特异性蛋白激酶家族的成员。它是一种参与调节肿瘤进展和细胞增殖的稀松蛋白/苏氨酸激酶。在这项研究中，研究了Dyrk 1B在乳腺癌发展中的作用。Western blot和免疫组化染色检测Dyrk 1B的表达，均证实Dyrk 1B在乳腺癌组织和细胞中过表达。统计学分析显示，Dyrk 1B表达的程度与多种临床病理因素相关，包括肿瘤大小、分级、雌激素受体状态和Ki-67表达，高表达预示预后不良。小干扰RNA（siRNA）敲除DYRKIB基因后，乳腺癌细胞的生长受到明显抑制。此外，FoxO 1可被Dyrk 1B磷酸化，然后由细胞核穿梭进入细胞质，这可能是Dyrk 1B介导乳腺癌细胞存活的机制。研究结果表明，Dyrk 1B在乳腺癌的进展中起着关键作用，并为乳腺癌的治疗提供了新的靶点。(C)2017由Elsevier Inc.出版
Dyrk1B, also called minibrain-related kinase (Mirk), is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk)/minibrain family of dual-specificity protein kinases. It is a scrim/threonine kinase involved in the regulation of tumor progression and cell proliferation. In this study, the role of Dyrk1B in breast cancer development was investigated. The expression of Dyrk1B was detected by Western blot and immunohistochemistry staining, both of which demonstrated that Dyrk1B was overexpressed in breast cancer tissues and cells. Statistical analysis showed that the extent,of Dyrk1B expression was associated with multiple clinicopathologic factors, including tumor size, grade, estrogen receptor status, and Ki-67 expression, and that high expression predicted a poor prognosis. The growth of breast cancer cells was inhibited significantly after knockout of DYRKIB by small interfering RNA (siRNA). Moreover, FoxO1 could be phosphorylated by Dyrk1B, and then FoxO1 was shuttled from the cell nucleus into the cytoplasm, which might be the mechanism of Dyrk1B-mediated survival in breast cancer cells. The results suggest that Dyrk1B plays a key role in the progression of breast cancer and provides a new target for breast cancer therapy. (C) 2017 Published by Elsevier Inc.