Abstract
A multifunctional scaffold protein termed Disabled-2 (Dab2) has recently gained attention in the scientific community and has emerged as a promising candidate in the realm of cancer research. Dab2 protein is involved in a variety of signaling pathways, due to which its significance in the pathogenesis of several carcinomas has drawn considerable attention. Dab2 is essential for controlling the advancement of cancer because it engages in essential signaling pathways such as the Wnt/β-catenin, epidermal growth factor receptor (EGFR), and transforming growth factor-beta (TGF-β) pathways. Dab2 can also repress epithelial-mesenchymal transition (EMT) which is involved in tumor progression with metastatic expansion and adds another layer of significance to its possible impact on cancer spread. Furthermore, the role of Dab2 in processes such as cell growth, differentiation, apoptosis, invasion, and metastasis has been explored in certain investigative studies suggesting its significance. The present review examines the role of Dab2 in the pathogenesis of various cancer subtypes including breast cancer, ovarian cancer, gastric cancer, prostate cancer, and bladder urothelial carcinoma and also sheds some light on its potential to act as a therapeutic target and a prognostic marker in the treatment of various carcinomas. By deciphering this protein’s diverse signaling, we hope to provide useful insights that may pave the way for novel therapeutic techniques and tailored treatment approaches in cancer management. Preclinical and clinical trial data on the impact of Dab2 regulation in cancer have also been included, allowing us to delineate role of Dab2 in tumor suppressor function, as well as its correlation with disease stage classification and potential therapy options. However, we observed that there is very scarce data in the form of studies on the evaluation of Dab2 role and treatment function in carcinomas, and further research into this matter could prove beneficial in the generation of novel therapeutic agents for patient-centric and tailored therapy, as well as early prognosis of carcinomas.
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Data availability
As our manuscript is review article, no new data were created or analyzed in this study. Data sharing does not apply to this article. However, the datasets/tables/figures generated during during the preparation of current manuscript are available from the corresponding author on reasonable request.
Abbreviations
- AMY:
-
Acute myeloid leukemia
- ADP:
-
Adenosine diphosphate
- AD:
-
Alzheimer’s disease
- AMPK:
-
AMP-activated protein kinase
- AR:
-
Androgen receptor
- APCs:
-
Antigen-presenting cells
- AIP1:
-
ASK1-interacting protein
- βCR:
-
β-Cell receptor
- BLOG:
-
Bioluminescent imaging
- CSC:
-
Cancer stem cell
- CPCs:
-
Cardiac progenitor cells
- CME:
-
Clathrin-mediated endocytosis
- CRISPR:
-
Clustered regularly interspaced short palindromic repeats
- Cas9:
-
CRISPR-associated protein 9
- CDK-2:
-
Cyclin-dependent kinase 2
- Dab2-Pser24:
-
Dab2-serine 24 phosphorylation
- DOC-2:
-
Differentially expressed ovarian carcinoma
- Dab2IP:
-
Disabled-2 interactive protein
- Dab2:
-
Disabled-2
- DFS:
-
Disease-free survival
- Dvl:
-
Disheveled
- Ddab:
-
Drosophila disabled
- EC:
-
Endothelial cell
- EGFR:
-
Epidermal growth factor receptor
- EMT:
-
Epithelial-to-mesenchymal transition
- ER’s:
-
Estrogen receptors
- ECM:
-
Extracellular matrix
- Foxp3:
-
Forkhead box P3
- Grb2:
-
Growth factor receptor-bound 2
- HCC:
-
Hepatocellular carcinoma
- HIF-1α:
-
Hypoxia-inducible factor 1
- LDL:
-
Low-density lipoprotein
- LUAD:
-
Lung adenocarcinoma
- LN:
-
Lymph node
- MAPK:
-
Mitogen-activated protein kinase
- NSCLC:
-
Non-small cell lung cancer
- OS:
-
Overall survival
- PDAC:
-
Pancreatic ductal adenocarcinoma
- PAMPs:
-
Pathogen-associated molecular patterns
- PTB:
-
Phosphotyrosine binding domain
- PFS:
-
Progression-free survival
- PRD:
-
Proline-rich domain
- Pca:
-
Prostate cancer
- PKC:
-
Protein kinase C
- QOL:
-
Quality of life
- Tregs:
-
Regulatory T-cells
- RT-qPCR:
-
Reverse transcriptase-quantitative polymerase chain reaction
- SNP:
-
Single nucleotide polymorphism
- SCLC:
-
Small cell lung cancer
- Tβrii:
-
TGF-beta (TGF–Β) type-II receptor
- TRAF:
-
TNF receptor-associated factor
- TLR:
-
Toll-like receptors
- TALEN:
-
Transcription activator-like effector nucleases
- TGF-β:
-
Transforming growth factor- β
- TAM:
-
Tumor-associated macrophages
- TME:
-
Tumor microenvironment
- UCB:
-
Urothelial carcinoma of the bladder
- VEGF:
-
Vascular growth factor
- WB:
-
Western blot
- Wnt:
-
Wingless-related integration site
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The authors are grateful to Prof. Gaurang B. Shah, Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India, for his kind support and guidance in manuscript preparation. The authors also extend their appreciation to the L. M. College of Pharmacy, Ahmedabad, India, for providing continuous library and resource support throughout the literature survey and data collection. The authors also extend their appreciation to the Sharaman Sci-Med Writing Association, India, for writing assistance at certain places and for providing continuous resources and support throughout the literature survey.
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Nidhi N. Shah, Bhavarth P. Dave, Kashvi C. Shah, Disha D. Shah, and Kunal G. Maheshwari: manuscript first draft preparation and subsequent editing, literature and data collection, analyzed the data, figures and diagram conception, designing, and wrote the manuscript. Mehul R. Chorawala: topic conception, design of content and skeleton, manuscript draft review and editing, figures and diagram conception, overall monitoring, and guidance throughout the study duration. Priyajeet Parekh and Maharsh Jani: manuscript draft review and editing, referencing, and improvising figures dpi. All the authors of this manuscript confirm that no paper mill and artificial intelligence was used.
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Nidhi N. Shah, Bhavarth P. Dave, Kashvi C. Shah, Disha D. Shah, and Kunal G. Maheshwari contributed equally to this work.
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Shah, N.N., Dave, B.P., Shah, K.C. et al. Disabled-2, a versatile tissue matrix multifunctional scaffold protein with multifaceted signaling: Unveiling its potential in the cancer battle. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03037-3
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DOI: https://doi.org/10.1007/s00210-024-03037-3