Cargando…

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

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: C...

Descripción completa

Detalles Bibliográficos
Autores principales: Mo, Xue-Tang, Leung, Thomas Ho-Yin, Tang, Hermit Wai-Man, Siu, Michelle Kwan-Yee, Wan, Peter Kok-Ting, Chan, Karen Kar-Loen, Cheung, Annie Nga-Yin, Ngan, Hextan Yuen-Sheung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463003/
https://www.ncbi.nlm.nih.gov/pubmed/32507856
http://dx.doi.org/10.1038/s41416-020-0922-7
_version_ 1783577035676844032
author Mo, Xue-Tang
Leung, Thomas Ho-Yin
Tang, Hermit Wai-Man
Siu, Michelle Kwan-Yee
Wan, Peter Kok-Ting
Chan, Karen Kar-Loen
Cheung, Annie Nga-Yin
Ngan, Hextan Yuen-Sheung
author_facet Mo, Xue-Tang
Leung, Thomas Ho-Yin
Tang, Hermit Wai-Man
Siu, Michelle Kwan-Yee
Wan, Peter Kok-Ting
Chan, Karen Kar-Loen
Cheung, Annie Nga-Yin
Ngan, Hextan Yuen-Sheung
author_sort Mo, Xue-Tang
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7463003
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-74630032021-06-08 CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma Mo, Xue-Tang Leung, Thomas Ho-Yin Tang, Hermit Wai-Man Siu, Michelle Kwan-Yee Wan, Peter Kok-Ting Chan, Karen Kar-Loen Cheung, Annie Nga-Yin Ngan, Hextan Yuen-Sheung Br J Cancer Article 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. Nature Publishing Group UK 2020-06-08 2020-09-01 /pmc/articles/PMC7463003/ /pubmed/32507856 http://dx.doi.org/10.1038/s41416-020-0922-7 Text en © The Author(s), under exclusive licence to Cancer Research UK 2020 https://creativecommons.org/licenses/by/4.0/Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Mo, Xue-Tang
Leung, Thomas Ho-Yin
Tang, Hermit Wai-Man
Siu, Michelle Kwan-Yee
Wan, Peter Kok-Ting
Chan, Karen Kar-Loen
Cheung, Annie Nga-Yin
Ngan, Hextan Yuen-Sheung
CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma
title CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma
title_full CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma
title_fullStr CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma
title_full_unstemmed CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma
title_short CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma
title_sort cd109 mediates tumorigenicity and cancer aggressiveness via regulation of egfr and stat3 signalling in cervical squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463003/
https://www.ncbi.nlm.nih.gov/pubmed/32507856
http://dx.doi.org/10.1038/s41416-020-0922-7
work_keys_str_mv AT moxuetang cd109mediatestumorigenicityandcanceraggressivenessviaregulationofegfrandstat3signallingincervicalsquamouscellcarcinoma
AT leungthomashoyin cd109mediatestumorigenicityandcanceraggressivenessviaregulationofegfrandstat3signallingincervicalsquamouscellcarcinoma
AT tanghermitwaiman cd109mediatestumorigenicityandcanceraggressivenessviaregulationofegfrandstat3signallingincervicalsquamouscellcarcinoma
AT siumichellekwanyee cd109mediatestumorigenicityandcanceraggressivenessviaregulationofegfrandstat3signallingincervicalsquamouscellcarcinoma
AT wanpeterkokting cd109mediatestumorigenicityandcanceraggressivenessviaregulationofegfrandstat3signallingincervicalsquamouscellcarcinoma
AT chankarenkarloen cd109mediatestumorigenicityandcanceraggressivenessviaregulationofegfrandstat3signallingincervicalsquamouscellcarcinoma
AT cheunganniengayin cd109mediatestumorigenicityandcanceraggressivenessviaregulationofegfrandstat3signallingincervicalsquamouscellcarcinoma
AT nganhextanyuensheung cd109mediatestumorigenicityandcanceraggressivenessviaregulationofegfrandstat3signallingincervicalsquamouscellcarcinoma