Critical role of SOX2-IGF2 signaling in aggressiveness of bladder cancer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 05 2020
19 05 2020
Historique:
received:
26
02
2019
accepted:
27
04
2020
entrez:
20
5
2020
pubmed:
20
5
2020
medline:
18
12
2020
Statut:
epublish
Résumé
Signaling elicited by the stem cell factors SOX2, OCT4, KLF4, and MYC not only mediates reprogramming of differentiated cells to pluripotency but has also been correlated with tumor malignancy. In this study, we found SOX2 expression signifies poor recurrence-free survival and correlates with advanced pathological grade in bladder cancer. SOX2 silencing attenuated bladder cancer cell growth, while its expression promoted cancer cell survival and proliferation. Under low-serum stress, SOX2 expression promoted AKT phosphorylation and bladder cancer cells' spheroid-forming capability. Furthermore, pharmacological inhibition of AKT phosphorylation, using MK2206, inhibited the SOX2-mediated spheroid formation of bladder cancer cells. Gene expression profiling showed that SOX2 expression, in turn, induced IGF2 expression, while SOX2 silencing inhibited IGF2 expression. Moreover, knocking down IGF2 and IGF1R diminished bladder cancer cell growth. Lastly, pharmacological inhibition of IGF1R, using linsitinib, also inhibited the SOX2-mediated spheroid formation of bladder cancer cells under low-serum stress. Our findings indicate the SOX2-IGF2 signaling affects the aggressiveness of bladder cancer cell growth. This signaling could be a promising biomarker and therapeutic target for bladder cancer intervention.
Identifiants
pubmed: 32427884
doi: 10.1038/s41598-020-65006-z
pii: 10.1038/s41598-020-65006-z
pmc: PMC7237425
doi:
Substances chimiques
IGF1R protein, human
0
KLF4 protein, human
0
Kruppel-Like Factor 4
0
SOX2 protein, human
0
SOXB1 Transcription Factors
0
Insulin-Like Growth Factor II
67763-97-7
Receptor, IGF Type 1
EC 2.7.10.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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