High Monopolar Spindle 1 Is Associated with Short Survival of Cholangiocarcinoma Patients and Enhances the Progression Via AKT and STAT3 Signaling Pathways

Biomedicines

Chawalit Pairojkul¹  Yaovalux Chamgramol¹  Worachart Lert-itthiporn²  Sopit Wongkham²  Kulthida Vaeteewoottacharn²  Piya Prajumwongs²  Ratthaphong Phumphu²  Orawan Waenphimai²  Kanlayanee Sawanyawisuth² 

[1] Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand;Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;

关键词: MPS1;    Cholangiocarcinoma;    migration;    invasion;    AKT;    STAT3;   

DOI  :  10.3390/biomedicines9010068

来源: DOAJ

【 摘 要 】

Cholangiocarcinoma (CCA) is a malignancy of the bile duct epithelium. The major problems of this cancer are late diagnosis and a high rate of metastasis. CCA patients in advanced stages have poor survival and cannot be cured with surgery. Therefore, targeting molecules involved in the metastatic process may be an effective CCA treatment. Monopolar spindle 1 (MPS1) is a kinase protein that controls the spindle assemble checkpoint in mitosis. It is overexpressed in proliferating cells and various cancers. The functional roles of MPS1 in CCA progression have not been investigated. The aims of this study were to examine the roles and molecular mechanisms of MPS1 in CCA progression. Immunohistochemistry results showed that MPS1 was up-regulated in carcinogenesis of CCA in a hamster model, and positive expression of MPS1 in human CCA tissues was correlated to short survival of CCA patients (n = 185). Small interfering RNA (siRNA)-induced knockdown of MPS1 expression reduced cell proliferation via G2/M arrest, colony formation, migration, and invasion. Moreover, MPS1 controlled epithelial to mesenchymal transition (EMT)-mediated migration via AKT and STAT3 signaling transductions. MPS1 was also involved in MMPs-dependent invasion of CCA cell lines. The current research highlights for the first time that MPS1 has an essential role in promoting the progression of CCA via AKT and STAT3 signaling pathways and could be an attractive target for metastatic CCA treatment.

【 授权许可】

Unknown