Sox2 induces tumorigenesis and angiogenesis of early-stage esophageal squamous cell carcinoma through secretion of Suprabasin.
Antigens, Differentiation
/ metabolism
Apoptosis
Biomarkers, Tumor
/ genetics
Carcinogenesis
/ metabolism
Cell Movement
Cell Proliferation
Esophageal Neoplasms
/ blood supply
Esophageal Squamous Cell Carcinoma
/ blood supply
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Proteins
/ metabolism
Neovascularization, Pathologic
/ metabolism
Phosphorylation
Prognosis
SOXB1 Transcription Factors
/ genetics
Signal Transduction
Tumor Cells, Cultured
Journal
Carcinogenesis
ISSN: 1460-2180
Titre abrégé: Carcinogenesis
Pays: England
ID NLM: 8008055
Informations de publication
Date de publication:
13 11 2020
13 11 2020
Historique:
received:
13
09
2019
revised:
27
01
2020
accepted:
12
02
2020
pubmed:
15
2
2020
medline:
27
5
2021
entrez:
15
2
2020
Statut:
ppublish
Résumé
Early stage of esophageal squamous cell carcinoma (ESCC) is known to be accompanied by angiogenesis and morphological changes of microvessels. Transcription factor Sox2 is amplified in various cancers including ESCC, but the role of Sox2 in the carcinogenesis and angiogenesis has not been determined. Hence, we aimed to investigate the role of Sox2 in the early stage of ESCC. We found that the expression of Sox2 was significantly higher in early-stage ESCC tissues than that in their adjacent normal tissues. We then established Sox2-inducible normal human esophageal squamous cell line (HetSox2) to investigate the role of Sox2 in esophageal carcinogenesis and angiogenesis in vitro. Sox2 overexpression led to increased cell proliferation and spheroid formation. The culture supernatant of Sox2-overexpressing HetSox2 induced migration and sprouting of endothelial cell line HUVEC (human umbilical vein endothelial cell). As for the mechanism, we found that the expression of secreted protein Suprabasin was directly induced by Sox2. Suprabasin enhanced proliferation of normal human esophageal squamous cells when added to the culture. Moreover, Suprabasin enhanced migration and sprouting of HUVEC cells, which were observed with the culture supernatant of Sox2-overexpressing HetSox2. This angiogenic effect of Suprabasin was abolished by inhibiting AKT phosphorylation, which suggested its dependence on AKT signaling. Finally, we showed that Suprabasin expression and the density of microvessels were significantly higher in ESCC tissues with high Sox2 expression. Our study suggested that increased Sox2 expression in esophageal squamous cells induced Suprabasin expression, and as a result initiated the carcinogenesis via increased cell proliferation and angiogenesis.
Identifiants
pubmed: 32055838
pii: 5735720
doi: 10.1093/carcin/bgaa014
doi:
Substances chimiques
Antigens, Differentiation
0
Biomarkers, Tumor
0
Neoplasm Proteins
0
SBSN protein, human
0
SOX2 protein, human
0
SOXB1 Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1543-1552Informations de copyright
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.