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CD109 通过调节宫颈鳞状细胞癌中的 EGFR 和 STAT3 信号转导来介导肿瘤发生和癌症侵袭性。

CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma.

机构信息

Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, Special Administrative Region of China.

Department of Pathology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, Special Administrative Region of China.

出版信息

Br J Cancer. 2020 Sep;123(5):833-843. doi: 10.1038/s41416-020-0922-7. Epub 2020 Jun 8.

DOI:10.1038/s41416-020-0922-7
PMID:32507856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7463003/
Abstract

BACKGROUND

CD109 was involved in the tumorigenesis and progression of various cancers via TGF-β1 signalling and STAT3 activation. As CD109 is strongly expressed in cervical squamous cell carcinoma, this study was conducted to investigate its functional characteristics in cervical cancer.

METHODS

CD109 expression was examined by immunohistochemistry (IHC) with cervical tissue microarray. The effects of CD109 expression were examined on migration, cell proliferation, spheroid formation and soft-agar colony-formation assay. Meanwhile, cervical cancer cell lines with high CD109 expression were chosen for the functional study using siRNA knockdown and CRISPR/Cas9 knockout.

RESULTS

IHC demonstrated an upregulation of CD109 in the cell membrane of cervical squamous cell carcinoma. CD109( + ) cells isolated by flow-cytometric sorting displayed enhanced migration, cell proliferation, sphere-forming and anchorage-independent cell growth ability. In contrast, silencing of CD109 expression could reverse the in vitro and in vivo tumorigenic and aggressive properties. Furthermore, CD109 induced EGFR-mediated STAT3 phosphorylation known to be responsible for cell migration, proliferation and maintenance of CSC phenotype.

CONCLUSION

Abundant CD109( + ) populations in cervical cancer cells potentially contributed to carcinogenesis and aggressiveness, whereas silencing of CD109 expression could reverse those properties. CD109 mediates cervical tumorigenicity and aggressiveness via CD109/EGFR/STAT3 signalling.

摘要

背景

CD109 通过 TGF-β1 信号和 STAT3 激活参与各种癌症的发生和进展。由于 CD109 在宫颈鳞状细胞癌中强烈表达，因此进行了这项研究，以研究其在宫颈癌中的功能特征。

方法

使用宫颈组织微阵列通过免疫组织化学（IHC）检查 CD109 的表达。通过迁移、细胞增殖、球体形成和软琼脂集落形成测定检查 CD109 表达的影响。同时，选择高 CD109 表达的宫颈癌细胞系，使用 siRNA 敲低和 CRISPR/Cas9 敲除进行功能研究。

结果

IHC 显示 CD109 在宫颈鳞状细胞癌的细胞膜中上调。通过流式细胞术分选分离的 CD109(+)细胞显示出增强的迁移、细胞增殖、球体形成和锚定非依赖性细胞生长能力。相反，沉默 CD109 表达可以逆转体外和体内的致瘤和侵袭特性。此外，CD109 诱导 EGFR 介导的 STAT3 磷酸化，已知该磷酸化负责细胞迁移、增殖和维持 CSC 表型。

结论

宫颈癌细胞中丰富的 CD109(+)群体可能有助于癌症发生和侵袭性，而沉默 CD109 表达可以逆转这些特性。CD109 通过 CD109/EGFR/STAT3 信号转导介导宫颈癌的致瘤性和侵袭性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/27b6527fa1d7/41416_2020_922_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/73f59ff75deb/41416_2020_922_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/09a10f433406/41416_2020_922_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/10a9b5f95ffb/41416_2020_922_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/f1f6d9f4d0da/41416_2020_922_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/33195c14927a/41416_2020_922_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/27b6527fa1d7/41416_2020_922_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/73f59ff75deb/41416_2020_922_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/09a10f433406/41416_2020_922_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/10a9b5f95ffb/41416_2020_922_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/f1f6d9f4d0da/41416_2020_922_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/33195c14927a/41416_2020_922_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/7463003/27b6527fa1d7/41416_2020_922_Fig6_HTML.jpg

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