Evaluating the Molecular Properties and Function of ANKHD1, and Its Role in Cancer
Abstract
:1. Structure and Function of ANKHD1
2. The Protein Domains of ANKHD1
3. Isoforms of ANKHD1
4. Post-Translational Modifications of ANKHD1
5. Subcellular Localisation of ANKHD1
6. Role of ANKHD1 in Signalling Pathways
6.1. SHP2 Signalling
6.2. JAK/STAT Signalling Pathway
6.3. Hippo Signalling Pathway
6.4. p21 Signalling Pathway
7. Role of ANKHD1 in Cancer
Type of Cancer | References | Cellular Function of ANKHD1 | Clinical Features Associated with Enhanced ANKHD1 |
---|---|---|---|
Breast Cancer | [10,38] | Increases the viability, clonogenicity and migration of aggressive breast cancer cell lines, possibly due to the positive regulation of the YAP/Yki pathway. | Increased levels of ANKHD1 were correlated with a reduction in relapse-free survival, but the extent differs based on the breast cancer subtype. |
Colorectal Cancer | [54] | Increases cell proliferation, migration, and invasion. It also dysregulates the epithelial organisation of tissues by increasing epithelial-to-mesenchymal transition. | ANKHD1 expression was correlated with greater tumour infiltration. It was demonstrated to promote metastasis and growth in tumorous nodules. |
Glioma | [17] | Promotes angiogenesis. | An increase in ANKHD1 is detected in glioma-associated endothelial cells, but there are no data to show how this may affect prognosis. |
Hepatocellular Cancer | [61] | Enhances cellular migration and invasion. | Higher levels of ANKHD1 are correlated with larger tumours, more nodes, poorer differentiation of tumour boundaries, more advanced metastasis, shorter time between recurrence and overall reduced survival rates. |
Leukaemia | [13,33] | Increases cellular and clonal proliferation and migration. It enhances tumorigenicity in xenografts. | Higher levels of ANKHD1 (protein and mRNA) are observed in leukaemia cell lines and (mRNA only) are observed in primary acute leukaemia samples. |
Non-Small-Cell Lung Cancer | [53,62] | Stimulates proliferation, invasion, and colony formation. May have a role in promoting DDP-chemoresistance. | ANKHD1 expression was correlated with greater growth, metastasis, overall reduced survival rates and poorer prognosis. ANKHD1 is required for SMYD3-induced DDP chemoresistance. |
Multiple Myeloma | [34,36,57] | Increases proliferation and cell-cycle progression. It enhances tumorigenicity in xenografts. It also promotes growth, division, and migration of cell colonies. | ANKHD1 is highly expressed in neoplastic plasma cells. |
Pancreatic Ductal Adenocarcinoma | [64,65] | Inferred control of cell growth by controlling the cell cycle inhibitor, p21. | Premature termination of the ANKHD1 protein due to a nonsense mutation (E2410*) was correlated with Pancreatic Ductal Adenocarcinoma. |
Prostate Cancer | [51] | Increases cell growth, cell cycle progression during S phase and enhances tumorigenicity in xenografts. | No data. |
Renal Cell Carcinoma | [16] | Increases proliferation by upregulating proliferative genes and drives cellular division via mitosis. | ANKHD1 expression (protein and mRNA) is upregulated early in the kidneys of patients with renal cell carcinoma. |
Uterine Corpus Endometrial Carcinoma | [37] | In murine models, transcript variant ANKHD1-BP3 was demonstrated to promote cell proliferation whilst inhibiting metastasis. | Transcript variant ANKHD1-BP3 was highly expressed in primary tissue samples. In clinical samples, it was demonstrated to promote proliferation but inhibit metastasis, invasion, apoptosis, and necrosis of cells. |
8. Summary and Concluding Remarks
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mullenger, J.L.; Zeidler, M.P.; Fragiadaki, M. Evaluating the Molecular Properties and Function of ANKHD1, and Its Role in Cancer. Int. J. Mol. Sci. 2023, 24, 12834. https://doi.org/10.3390/ijms241612834
Mullenger JL, Zeidler MP, Fragiadaki M. Evaluating the Molecular Properties and Function of ANKHD1, and Its Role in Cancer. International Journal of Molecular Sciences. 2023; 24(16):12834. https://doi.org/10.3390/ijms241612834
Chicago/Turabian StyleMullenger, Jordan L., Martin P. Zeidler, and Maria Fragiadaki. 2023. "Evaluating the Molecular Properties and Function of ANKHD1, and Its Role in Cancer" International Journal of Molecular Sciences 24, no. 16: 12834. https://doi.org/10.3390/ijms241612834