CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma
Menée in vitro et à l'aide d'une xénogreffe de carcinome épidermoïde du col utérin sur un modèle murin, cette étude met en évidence un mécanisme par lequel l'antigène CD109 favorise la carcinogenèse et l'agressivité de la tumeur via la régulation de la signalisation du récepteur EGFR et du facteur de transcription STAT3
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
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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
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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.