STAT3 mediates RCP-induced cancer cell invasion through the NF-κB/Slug/MT1-MMP signaling cascade.
Arch Pharm Res
; 45(7): 460-474, 2022 Jul.
Article
em En
| MEDLINE
| ID: mdl-35809175
ABSTRACT
Rab coupling protein (RCP) has been known to induce cancer invasion and metastasis, and STAT3 is one of major oncogenic factors. In the present study, we identify the critical role of STAT3 in RCP-induced cancer cell invasion. Immunohistochemical data of ovarian cancer tissues presented that levels of RCP expression are closely correlated with those of phospho-STAT3 (p-STAT3). In addition, ovarian cancer patients with high expression of both RCP and p-STAT3 had significantly lower progress-free and overall survival rates compared to those with low either RCP or p-STAT3 expression. Mechanistically, RCP induced STAT3 phosphorylation in both ovarian and breast cancer cells. Silencing or pharmacological inhibition of STAT3 significantly inhibited RCP-induced cancer cell invasion. In addition, we provide evidence that the ß1 integrin/EGFR axis is important for RCP-induced STAT3 phosphorylation. Furthermore, STAT3 activated NF-κB for Slug expression that in turn upregulated MT1-MMP expression for cancer cell invasion. Collectively, our present data demonstrate that STAT3 is located downstream of the ß1 integrin/EGFR axis and induces Slug and MT1-MMP expression for cancer cell invasion.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
NF-kappa B
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Arch Pharm Res
Ano de publicação:
2022
Tipo de documento:
Article