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Dishevelled: An emerging therapeutic oncogene in human cancers
Shadia Hamoud Alshahrani1, Nodir Rakhimov2, Arti Rana3
1Medical Surgical Nursing Department, King Khalid University, Khamis Mushate, Saudi Arabia.
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.
Insights
Dishevelled (DVL) protein promotes cancer progression by enhancing cell invasion, survival, and metastasis. Elevated DVL levels may serve as a diagnostic and prognostic biomarker and mediate chemoresistance in various cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cancer is characterized by uncontrolled cell proliferation and metastasis.
- The Wnt signaling pathway plays a critical role in cancer development and progression.
- Dishevelled (DVL) is a key regulator in both canonical and non-canonical Wnt signaling pathways.
Purpose of the Study:
- To investigate the molecular mechanisms underlying DVL's role in cancer pathogenesis.
- To explore the potential of DVL as a diagnostic and prognostic biomarker in cancer.
- To examine DVL's involvement in mediating chemoresistance to common cancer therapeutics.
Main Methods:
- Analysis of DVL expression levels in cancer cell lines and clinical specimens.
- Investigation of DVL's functional impact on cancer cell behaviors such as invasion, migration, and apoptosis.
- Correlation analysis between DVL expression and clinicopathological features of cancer patients.
- Assessment of DVL's role in chemoresistance to Methotrexate, paclitaxel, and 5-fluorouracil.
Main Results:
- Increased DVL expression was observed in various cancer types, correlating with aggressive clinicopathological characteristics.
- DVL was found to promote cell invasion, migration, proliferation, survival, stemness, and epithelial-mesenchymal transition (EMT), while suppressing apoptosis.
- Higher DVL levels were associated with lymph node metastasis, advanced tumor grade, and specific histological types.
- DVL demonstrated a role in mediating chemoresistance to Methotrexate, paclitaxel, and 5-fluorouracil.
Conclusions:
- DVL exhibits oncogenic properties, driving key aspects of cancer progression and metastasis.
- DVL represents a promising biomarker for cancer diagnosis and prognosis.
- Targeting DVL may offer a therapeutic strategy to overcome chemoresistance in cancer treatment.
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