Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis
| Autor: | Chun Peng, Vu Hong Loan Nguyen, Stefanie Bernaudo, Rebecca Hough |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
cancer stem cells endocrine system diseases Carcinogenesis Review Biology medicine.disease_cause lcsh:Gynecology and obstetrics Metastasis 03 medical and health sciences Ovarian tumor 0302 clinical medicine Downregulation and upregulation Cancer stem cell Ovarian cancer microRNA medicine Animals Humans metastasis Wnt Signaling Pathway beta Catenin lcsh:RG1-991 Ovarian Neoplasms Wnt signaling pathway Obstetrics and Gynecology tumor angiogenesis medicine.disease female genital diseases and pregnancy complications 3. Good health microRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Female Wnt/β-catenin signalling |
| Zdroj: | Journal of Ovarian Research, Vol 12, Iss 1, Pp 1-17 (2019) Journal of Ovarian Research |
| ISSN: | 1757-2215 |
| Popis: | Epithelial ovarian cancer (EOC) is the deadliest female malignancy. The Wnt/β-catenin pathway plays critical roles in regulating embryonic development and physiological processes. This pathway is tightly regulated to ensure its proper activity. In the absence of Wnt ligands, β-catenin is degraded by a destruction complex. When the pathway is stimulated by a Wnt ligand, β-catenin dissociates from the destruction complex and translocates into the nucleus where it interacts with TCF/LEF transcription factors to regulate target gene expression. Aberrant activation of this pathway, which leads to the hyperactivity of β-catenin, has been reported in ovarian cancer. Specifically, mutations ofCTNNB1,AXIN, or APC,have been observed in the endometrioid and mucinous subtypes of EOC. In addition, upregulation of the ligands, abnormal activation of the receptors or intracellular mediators, disruption of the β-catenin destruction complex, inhibition of the association of β-catenin/E-cadherin on the cell membrane, and aberrant promotion of the β-catenin/TCF transcriptional activity, have all been reported in EOC, especially in the high grade serous subtype. Furthermore, several non-coding RNAs have been shown to regulate EOC development, in part, through the modulation of Wnt/β-catenin signalling. The Wnt/β-catenin pathway has been reported to promote cancer stem cell self-renewal, metastasis, and chemoresistance in all subtypes of EOC. Emerging evidence also suggests that the pathway induces ovarian tumor angiogenesis and immune evasion. Taken together, these studies demonstrate that the Wnt/β-catenin pathway plays critical roles in EOC development and is a strong candidate for the development of targeted therapies. |
| Databáze: | OpenAIRE |
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