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- Table of Contents
Facts about Aldehyde dehydrogenase, dimeric NADP-preferring.
Oxidizes medium and long chain aldehydes into non-toxic fatty acids (PubMed:1737758). Preferentially oxidizes aromatic aldehyde substrates (PubMed:1737758).
Human | |
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Gene Name: | ALDH3A1 |
Uniprot: | P30838 |
Entrez: | 218 |
Belongs to: |
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aldehyde dehydrogenase family |
aldehyde dehydrogenase 3 family, member A1; Aldehyde dehydrogenase 3; Aldehyde Dehydrogenase 3A1; Aldehyde Dehydrogenase 3-A1; Aldehyde dehydrogenase family 3 member A1; aldehyde dehydrogenase isozyme 3; aldehyde dehydrogenase type III; ALDH3A1; ALDH3aldehyde dehydrogenase, dimeric NADP-preferring; ALDHIII; EC 1.2.1; EC 1.2.1.5; MGC10406; stomach aldehyde dehydrogenase
Mass (kDA):
50.395 kDA
Human | |
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Location: | 17p11.2 |
Sequence: | 17; NC_000017.11 (19737984..19748390, complement) |
High levels in stomach, esophagus and lung; low level in the liver and kidney.
Cytoplasm.
The ALDH3A1 CSC marker has clinical applications. Its high prevalence is linked to the evolution in gastric cancer. This study was supported in part by the Chinese Medicine Research Program (grant numbers: LY15h260030 & LY15h260031).
The role of ALDH in the progression of solid tumors is becoming clearer. ALDH is associated to aggressive stem-like cell (cSCs) as well as a number of important cellular processes such expansion and metastasis. However, it remains to be determined if ALDH plays a role in metastasis. ALDH may play a significant role in this process according to experimental evidence and data from animal models and in vitro studies.
To understand the molecular mechanism of the ALDH3A1 marker in cancer, we have extensively studied it. This has resulted in the identification of a number of co-expressed molecular genes and signaling pathways. The Hedgehog pathway was identified in 2007 as a candidate for association to ALDH-positive pancreatic cancer cells. ALDH expression in tumor-associated epithelial cells has been linked to an increase in angiogenic activity.
The ALDH enzyme's wide distribution in tumors is a major hurdle to its targeting. Despite this widespread distribution, the differential epigenetic landscapes make it an unreliable pharmacological target. It is highly expressed within the liver and kidney, but it is difficult to determine which isoform is best for druggability. ALDH's enzymatic, oxidative reaction is highly non-specific. Nonspecific inhibitors can cause toxic side effects.
In addition to the role of ALDH in tumor growth, ALDH has also been implicated in cancer cell self-protection. ALDH is thought, because of its role NADPH-recycling, to increase the antioxidant capacity of cancer cells. Furthermore, ALDH co-expresses with other antioxidant factors and drug efflux channels. Different enzymes in the ALDH family play different roles in detoxifying lipid peroxidation products.
Further comparative studies of ALDH are necessary to determine whether ALDH is a better stem cell marker. ALDH may be more effective in certain applications and could even serve as a marker for CSCs in different types of cancer. However, scientists will have more information about ALDH isozymes to help them develop new strategies for cancer and regenerative medicine.
Cisplatin can increase ALDH3A1 expression within a variety of cancer cells. Alda-89 was found to be a small molecule that has a molecular mass of 162.1 and was intra-tumorily used in SCC4- and PCI-13 cells. Aldi-6 treatment decreased cell viability in both types of cells and in vivo inhibited tumor development. Aldi-6 also inhibits ALDH3A1 expression in PCI-13- and SCC4 cell lines.
ALDH activity was also identified in a variety tissue types. It is capable of distinguishing between cancer cells. This suggests that ALDH3A1's role in tumorigenesis may be multifaceted. The ALDEFLUOR(tm), a test that differentiates cancer cell subpopulations using their altered activity levels, can be used to do so. ALDH3A1 can also be associated with multiple tumor-sponsoring types.
A new protein, ALDH3A1, has recently been developed and was tested in clinical trials to prove its anti-cancer properties. This protein was expressed as a human recombinant and purified with nickel column chromatography. Its function was analyzed using the Kaplan-Meier plotter and GEO. The results were compared to other studies and showed a greater correlation with a poor outcome among patients with hepatitis C.
We used the ALDH3A1 gene transcription to study anti-aldehyde genes (ALDHs). The study involved 92 patients with lung cancer, squamous cell carcinoma or both. The gene expression levels of each sample were compared and the Kaplan-Meier survival curves were compared. Poor outcomes were associated with the expression of ALDH3A1 in each group. Researchers also examined the effects of ALDH3A1 and the tumor's response against chemotherapy.
Additionally, it has been proven that ALDH3A1 activators can be used to prevent hyposalivation caused by radiation exposure in patients with head or neck cancer. This study proved that activators can prevent the production of the enzyme from tumor cells. This study supports the use redox-sensitive medications in clinical trials. Although these drugs are not currently available for clinical trial, it is possible that a therapeutic agent may be found.
Sustaining ALDH3A1 activity after RT improved salivary function in mice, as did the use Alda-341 drug. The study also showed that SSPC with a deficiency in ALDH3A1 were less likely form spheres than those without ALDH3A1.
Aldehyde dehydrogenase activity was shown to be a hallmark for cancer stem cells. It is unknown if this enhanced activity depends on the ALDH-isoform. ALDHbright cell lines from two human gastric tumor cell lines showed increased self-renewal as well as differentiation and tumorigenicity. The findings are important because it offers new insight into the mechanisms that promote cancer stem cells.
ALDH3A1 activity is essential for the self-renewal and embryonic differentiation of adult salivary stem cells. It also maintains mitochondria's number and function. ALDH3A1 deficiency results in altered tissue structure. ALDH3A1 activators can help stem cells recover their ability to differentiate following radiation treatment. This marker is important in many clinical trials, including breast cancer.
Clinical trials are also important because it is the endpoint that determines whether a patient will survive. Alternative ways to assess survival benefits include progression-free survival. A new study has examined the relationship between HCSC marks and a patient’s risk for poor prognosis. A poor prognosis is also associated to high levels of ALDH3A1.
The expression levels of ALDh2A1 were varying between 0 and 3. This gene has a positive correlation to the proliferation rate. In pancreatic tumour samples, the cytoplasmic ALDh2A11 expression was 0.5 to 1 in BxPC3, B3M4, and Pann1, respectively. AsPC-1, SU8686, Colo-357, and Colo-357 showed higher expression.
Patients with lung tumors were able to survive with and without augmented ALDH3A1 expression. The survival rates were the same for ALDh2+ and -negative patients. Patients with augmented ALDh2A1 did not have a significant survival rate. Although ALDh2+ patients had a lower survival ratio than CD133-positive, it was still statistically significant.
There is increasing evidence that ALDh2A1 can be used as a CSC marker. ALDh2A1 may play a significant part in tumor cell expansion, but other ALDH isoforms could also increase resistance to chemotherapy. Furthermore, the tumor-related role of ALDH is less understood. ALDH3A1 is also a potential therapeutic target in cancer metastasis.
Although ALDH3A1 has shown promise in breast cancer research, the gene's expression has not been thoroughly studied. However, ALDh2A1 has also been implicated in colon cancer and lung cancer. It is important in determining disease progression because it is associated with drug resistance. Although ALDh2A1A1 (and ALDH2) are widely recognized for being cancer markers, the clinical implications of their existence are less clear.
A recent study that included 12 patients with CRC discovered that ALDh2-CD133 had a significant correlation in patient prognosis. However, more research is needed in order to confirm this correlation. In addition, ALDh2 as well as CD133 have important clinical implications for the development of a novel treatment strategy to target CRCs. There are many reasons CD133 or ALDh2 could be of use.
Recent research revealed that ALDH3A1 had been detected in the cells' cytoplasm. Low levels of ALDH3A1 expression in CRC tissue showed a significant difference, with low levels corresponding to a small percentage of patients. Moreover, there were several patients who had no ALDH3A1 staining at all. Three genes were also identified by the researchers as being associated with low ALDH3A1 levels.
Tumor cells of all grade express the ALDh2A1 proteins. Study results showed that tumor grade decreased with higher levels of ALDh2 protein expression. This was consistent with Dukes' staging. Patients with high levels of ALDh2 expression had shorter survival times than patients with lower expression. A marker for CSCs might also be high ALDH3A1 levels.
Another study showed that ALDH3A1 was positively associated for metastatic activity of breast-cancer cells. The ALDH3A1 overexpression was also associated to the presence of an ALDH3A1-positive tumor-suppressor (ENDOU) gene. These findings support the hypothesis that breast cancer metastatic activity can be associated with the ALDH3A1 genotype.
PMID: 1737758 by Hsu L.C., et al. Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli.
PMID: 8493892 by Hsu L.C., et al. Human stomach aldehyde dehydrogenase, ALDH3.