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Wnt-LRP5信号通路的失活抑制卵巢癌细胞的增殖和迁移。

Inactivation of Wnt-LRP5 signaling suppresses the proliferation and migration of ovarian cancer cells.

作者信息

Hong Jing, Xie Zeyu, Yang Zhihua, Yang Fangyao, Liao Hai, Rao Shuquan, Huang Xinhe

机构信息

School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.

出版信息

Transl Cancer Res. 2021 May;10(5):2277-2285. doi: 10.21037/tcr-20-3462.

DOI:10.21037/tcr-20-3462
PMID:35116545
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8797788/
Abstract

BACKGROUND

Ovarian cancer (OCa) is the most lethal gynecological malignant tumor, with few or no specific symptoms in its early stage. There are many signaling pathways involved in the process of OCa progression, among which the highly complex Wnt signaling pathway plays a unique role in the occurrence and development of OCa because of its functions of regulating gene expression, cell proliferation, migration, and invasion. Lipoprotein associated receptor protein 5/6 (LRP5/6) binds to activate this key pathway. Therefore, it is very important to study the mechanism of Wnt-LRP5 signaling pathway in the proliferation and migration of OCa.

METHODS

In the present study, we have investigated the role of Wnt-LRP5 signaling pathway in OCa proliferation and migration for the first time using the dominant negative plasmid of LRP5 (DN-LRP5) and human OCa cells HO8910PM plus in a mouse model.

RESULTS

Our data showed inactivation of LRP5 resulted in shift of epithelial-mesenchymal transition (EMT), rearrangement of the cytoskeleton, lowered activity of pro-proliferation and pro-migration cancer signaling pathways including Akt, p38 and NF-κB, eventually decreased proliferation and migration of OCa cells HO8910PM . Moreover, OCa-DN-LRP5 mouse model developed significantly smaller tumors as determined by inoculation of HO8910PM-DN-LRP5 cells into nude mice.

CONCLUSIONS

Collectively, our results demonstrate the dominant role of Wnt-LRP5 in OCa proliferation and migration and its potential as a valuable therapeutic target.

摘要

背景

卵巢癌（OCa）是最致命的妇科恶性肿瘤，早期几乎没有特异性症状。OCa进展过程涉及许多信号通路，其中高度复杂的Wnt信号通路因其在调节基因表达、细胞增殖、迁移和侵袭方面的功能，在OCa的发生和发展中发挥独特作用。脂蛋白相关受体蛋白5/6（LRP5/6）结合并激活这一关键通路。因此，研究Wnt-LRP5信号通路在OCa增殖和迁移中的机制非常重要。

方法

在本研究中，我们首次使用LRP5显性负性质粒（DN-LRP5）和人OCa细胞HO8910PM加小鼠模型，研究Wnt-LRP5信号通路在OCa增殖和迁移中的作用。

结果

我们的数据显示，LRP5失活导致上皮-间质转化（EMT）转变、细胞骨架重排、包括Akt、p38和NF-κB在内的促增殖和促迁移癌症信号通路活性降低，最终降低了OCa细胞HO8910PM的增殖和迁移。此外，通过将HO8910PM-DN-LRP5细胞接种到裸鼠体内确定，OCa-DN-LRP5小鼠模型形成的肿瘤明显更小。

结论

总体而言，我们的结果证明了Wnt-LRP5在OCa增殖和迁移中的主导作用及其作为有价值治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/4f697aef6321/tcr-10-05-2277-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/4397edfa581c/tcr-10-05-2277-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/49d42d5c34f6/tcr-10-05-2277-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/056ba2e073bf/tcr-10-05-2277-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/4f697aef6321/tcr-10-05-2277-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/4397edfa581c/tcr-10-05-2277-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/49d42d5c34f6/tcr-10-05-2277-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/056ba2e073bf/tcr-10-05-2277-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/8797788/4f697aef6321/tcr-10-05-2277-f4.jpg

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