| Autor: |
McLean ME; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada., MacLean MR; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada., Cahill HF; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada., Arun RP; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada., Walker OL; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada., Wasson MD; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada., Fernando W; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada., Venkatesh J; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada., Marcato P; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada.; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada.; Nova Scotia Health Authority, Halifax, NS B3H 4R2, Canada. |
| Abstrakt: |
Aldehyde dehydrogenase 1A3 (ALDH1A3) is one of 19 ALDH enzymes expressed in humans, and it is critical in the production of hormone receptor ligand retinoic acid (RA). We review the role of ALDH1A3 in normal physiology, its identification as a cancer stem cell marker, and its modes of action in cancer and other diseases. ALDH1A3 is often over-expressed in cancer and promotes tumor growth, metastasis, and chemoresistance by altering gene expression, cell signaling pathways, and glycometabolism. The increased levels of ALDH1A3 in cancer occur due to genetic amplification, epigenetic modifications, post-transcriptional regulation, and post-translational modification. Finally, we review the potential of targeting ALDH1A3, with both general ALDH inhibitors and small molecules specifically designed to inhibit ALDH1A3 activity. |
