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NMIIA 通过激活胰腺癌中的 Wnt/β-连环蛋白信号通路和 EMT 促进肿瘤生长和转移。

NMIIA promotes tumor growth and metastasis by activating the Wnt/β-catenin signaling pathway and EMT in pancreatic cancer.

机构信息

Department of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

Oncogene. 2019 Jul;38(27):5500-5515. doi: 10.1038/s41388-019-0806-6. Epub 2019 Apr 9.

Abstract

Non-muscle myosin IIA (NMIIA) protein plays an important role in cell cytokinesis and cell migration. The role and underlying regulatory mechanisms of NMIIA in pancreatic cancer (PC) remain elusive. We found that NMIIA is highly expressed in PC tissues and contributes to PC poor progression by using open microarray datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and PC tissue arrays. NMIIA regulates β-catenin mediated EMT to promote the proliferation, migration, invasion, and sphere formation of PC cells in vitro and in vivo. NMIIA controls the β-catenin transcriptional activity by interacting with β-catenin. Moreover, MEK/ERK signaling is critical in MLC2 (Ser19) phosphorylation, which can mediate NMIIA activity and regulate Wnt/β-catenin signaling. These findings highlight the significance of NMIIA in tumor regression and implicate NMIIA as a promising candidate for PC treatment.

摘要

非肌肉肌球蛋白 IIA(NMIIA)蛋白在细胞胞质分裂和细胞迁移中发挥重要作用。NMIIA 在胰腺癌(PC)中的作用和潜在调节机制仍不清楚。我们使用来自基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)和 PC 组织芯片的公开微阵列数据集发现,NMIIA 在 PC 组织中高度表达,并通过促进β-连环蛋白介导的 EMT 促进 PC 细胞的增殖、迁移、侵袭和球体形成,从而导致 PC 不良进展。NMIIA 通过与β-连环蛋白相互作用来控制β-连环蛋白的转录活性。此外,MEK/ERK 信号通路在 MLC2(Ser19)磷酸化中起关键作用,该磷酸化可介导 NMIIA 活性并调节 Wnt/β-连环蛋白信号通路。这些发现强调了 NMIIA 在肿瘤消退中的重要性,并暗示 NMIIA 是 PC 治疗的有前途的候选药物。

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