Nucleolar and spindle associated protein 1 promotes metastasis of cervical carcinoma cells by activating Wnt/ß-catenin signaling.
J Exp Clin Cancer Res
; 38(1): 33, 2019 Jan 24.
Article
en En
| MEDLINE
| ID: mdl-30678687
ABSTRACT
BACKGROUND:
The primary obstacle to treat cervical cancer is its high prevalence of metastasis, which severely affects patients' quality of life and survival time. Nucleolar and spindle associated protein 1 (NUSAP1) has been implicated in the development, progression, and metastasis in several types of cancer. However, its oncogenic role in cervical cancer remains unclear.METHODS:
Western blot assay and immunohistochemistry were used to determine the expression of NUSAP1 in 21 clinical fresh Cervical cancer tissues and 233 clinicopathologically characterized cervical cancer specimens. The biological roles of NUSAP1 in the metastasis of cervical cancer were investigated both in vitro by EMT, Side population analysis and Transwell assays and so on, and in vivo using a mouse 4w model of hematogenous metastasis and lymph node metastasis. Bioinformatics analysis, luciferase reporter analysis, immunoprecipitation and immunoblotting of nuclear and cytoplasmic cellular fractions were applied to discern and examine the relationshipbetween NUSAP1 and its potential targets.RESULTS:
The results demonstrated that NUSAP1 was upregulated in cervical cancer cells and tissues, correlated positively with metastasis and poor clinical outcome of patients. High expression of NUSAP1 promoted metastasis by enhancing cancer stem cell (CSC) traits and epithelial-mesenchyme transition (EMT) progression, while silencing of NUSAP1 reduced CSC traits and EMT progression. Mechanistically, upregulation of NUSAP1 induced SUMOylation of TCF4 via interacting with SUMO E3 ligase Ran-binding protein 2 (RanBP2) and hyperactivated Wnt/ß-catenin signaling in cervical cancer cells. Additionally, NUSAP1-induced cervical cancer cells metastasis and the cancer stem cell phenotype were abrogated with the Wnt/ß-catenin signaling inhibitor XAV-939 treatment. Importantly, co-therapy of conventional treatment and XAV-939 will provide a novel and effective treatment for NUSAP1-ovexpressed cervical cancer patients.CONCLUSIONS:
Our results demonstrate thatNUSAP1 upregulation contributes to metastasis of cervical cancer by promoting CSC properties and EMT via Wnt/ß-catenin signaling and XAV-939 might serve as a potential tailored therapeutic option for patients with NUSAP1-ovexpressed cervical cancer.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pronóstico
/
Biomarcadores de Tumor
/
Neoplasias del Cuello Uterino
/
Proteínas Asociadas a Microtúbulos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Exp Clin Cancer Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
China