SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling.
Animals
Apoptosis
Biomarkers, Tumor
/ genetics
Carcinoma, Renal Cell
/ genetics
Cell Proliferation
Cell Transformation, Neoplastic
Female
Gene Expression Regulation, Neoplastic
HMG-Box Domains
Humans
Kidney Neoplasms
/ genetics
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Prognosis
SOXD Transcription Factors
/ genetics
Survival Rate
Tumor Cells, Cultured
Wnt1 Protein
/ genetics
Xenograft Model Antitumor Assays
beta Catenin
/ genetics
HMG domain
SOX6
Wnt/β-catenin
clear cell renal cell carcinoma
tumor suppressor
Journal
Molecular carcinogenesis
ISSN: 1098-2744
Titre abrégé: Mol Carcinog
Pays: United States
ID NLM: 8811105
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
27
03
2020
revised:
26
07
2020
accepted:
05
08
2020
pubmed:
15
8
2020
medline:
3
11
2020
entrez:
15
8
2020
Statut:
ppublish
Résumé
Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.
Substances chimiques
Biomarkers, Tumor
0
CTNNB1 protein, human
0
SOX6 protein, human
0
SOXD Transcription Factors
0
WNT1 protein, human
0
Wnt1 Protein
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1159-1173Informations de copyright
© 2020 Wiley Periodicals LLC.
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