Yao Qian, An Yu, Hou Wei, Cao Ya-Nan, Yao Meng-Fei, Ma Ning-Ning, Hou Lin, Zhang Hong, Liu Hai-Jing, Zhang Bo
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Oncotarget. 2017 Nov 30;8(65):109632-109645. doi: 10.18632/oncotarget.22759. eCollection 2017 Dec 12.
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 . 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.
低密度脂蛋白（LDL）受体相关蛋白6（LRP6）是Wnt信号通路的重要共受体，在结直肠癌的发生和发展中起主要作用。最近，LRP6失调已被证明与癌症进展有关，但其在结直肠癌中的生物学作用和临床意义仍不清楚。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分期相关，且预后较差。此外，磷酸化的LRP6与β-连环蛋白的核积累呈正相关。LRP6的过表达或激活可激活Wnt信号并促进肿瘤细胞迁移。LRP6的激活可能通过调节微管相关蛋白1B（MAP1B）、微管肌动蛋白交联因子1（MACF1）和Rho GTP酶——RhoA和Rac1来诱导微管动力学和肌动蛋白重塑。该研究表明，LRP6可能是结直肠癌进展中的潜在预后标志物和治疗靶点。
