LRP6 promotes invasion and metastasis of colorectal cancer through cytoskeleton dynamics.
LRP6 promotes invasion and metastasis of colorectal cancer through cytoskeleton dynamics.
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LRP6通过细胞骨架动力学促进结直肠癌侵袭和转移
DOI：
10.18632/oncotarget.22759
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发表时间：
2017-12-12
期刊：
影响因子：
--
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Yao Q;An Y;Hou W;Cao YN;Yao MF;Ma NN;Hou L;Zhang H;Liu HJ;Zhang B
低密度脂蛋白（LDL）受体相关蛋白-6 （LRP6）是Wnt通路的重要共受体，在结直肠癌的发生发展中起主导作用。近年来，LRP6的失调被证明参与了癌症的进展，但其在结直肠癌中的生物学作用和临床意义尚不清楚。在本研究中，我们发现LRP6的磷酸化在结直肠癌中异常上调，与TNM或Dukes分期和较差的预后相关。此外，磷酸化的LRP6与细胞核中β-catenin的积累呈正相关。过表达或激活LRP6可激活Wnt信号，促进肿瘤细胞在体外的迁移。LRP6的激活可能通过调控微管相关蛋白1B （MAP1B）、微管肌动蛋白交联因子1 （MACF1）和Rho GTPase——RhoA和Rac1来诱导微管动力学和肌动蛋白重塑。该研究提示LRP6可能是结直肠癌进展的潜在预后标志物和治疗靶点。
Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis. In addition, phosphorylated LRP6 was positively correlated with nuclear accumulation of β-catenin. Overexpression or activation of LRP6 could activate Wnt signaling and promote tumor cell migration in vitro. The activation of LRP6 could induce microtubule dynamics and actin remodeling, probably through regulation of microtubule-associated protein 1B (MAP1B), microtubule actin cross-linking factor 1 (MACF1) and Rho GTPase--RhoA and Rac1. The investigation suggests that LRP6 may be a potential prognostic marker and therapeutic target in the progression of colorectal cancers.
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影响因子：
3.5
作者：
Barnat, Monia;Benassy, Marie-Noelle;Nothias, Fatiha
通讯作者：
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影响因子：
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作者：
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