KIF2C: a novel link between Wnt/ß-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma.
Protein Cell
; 12(10): 788-809, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-32748349
ABSTRACT
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/ß-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/ß-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/ß-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cinesinas
/
Carcinoma Hepatocelular
/
Péptidos y Proteínas de Señalización Intracelular
/
Beta Catenina
/
Transición Epitelial-Mesenquimal
/
Neoplasias Hepáticas
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Protein Cell
Asunto de la revista:
BIOQUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China