Dishevelled: An emerging therapeutic oncogene in human cancers

Abstract

Cancer is a multifaceted and complex disorder characterized by uncontrolled rates of cell proliferation and its ability to spread and attack other organs. Emerging data indicated several pathways and molecular targets are engaged in cancer progression. Among them, the Wnt signaling pathway was shown to have a crucial role in cancer onset and progression. Dishevelled (DVL) acts in a branch point of canonical and non-canonical Wnt pathway. DVL not only acts in the cytoplasm to inactivate the destruction complex of β-catenin but is also transported into the nucleus to affect the transcription of target genes. Available data revealed that the expression levels of DVL increased in cell and clinical specimens of various cancers, proposing that it may have an oncogenic role. DVL promoted cell invasion, migration, cell cycle, survival, proliferation, 3D-spheroid formation, stemness, and epithelial mesenchymal transition (EMT) and it suppressed cell apoptosis. The higher levels of DVL is associated with the clinicopathological characteristic of cancer-affected patients, including lymph node metastasis, tumor grade, histological type, and age. In addition, the higher levels of DVL could be a promising diagnostic and prognostic biomarker in cancer as well as it could be a mediator in cancer chemoresistance to Methotrexate, paclitaxel, and 5-fluorouracil. This study aimed to investigate the underlying molecular mechanism of DVL in cancer pathogenesis as well as to explore its importance in cancer diagnosis and prognosis as well as its role as a mediator in cancer chemotherapy.

Keywords: Biomarker; Cancer; Chemoresistance; Dishevelled.