Genomes and Genes
Summary: A metalloflavoprotein enzyme involved the metabolism of VITAMIN A, this enzyme catalyzes the oxidation of RETINAL to RETINOIC ACID, using both NAD+ and FAD coenzymes. It also acts on both the 11-trans- and 13-cis-forms of RETINAL.
- Dupé V, Matt N, Garnier J, Chambon P, Mark M, Ghyselinck N. A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment. Proc Natl Acad Sci U S A. 2003;100:14036-41 pubmed..This malformation, which is similar to isolated congenital CA in humans and may result from impaired RA-controlled down-regulation of Fgf8 expression in nasal fins, can be prevented by a simple maternal treatment with RA...
- Bowles J, Feng C, Knight D, Smith C, Roeszler K, Bagheri Fam S, et al. Male-specific expression of Aldh1a1 in mouse and chicken fetal testes: implications for retinoid balance in gonad development. Dev Dyn. 2009;238:2073-80 pubmed publisher..Our data suggest that low levels of RA may be required for early developmental events in the testis, or that Aldh1a1 expression in the fetus may prefigure a later requirement for ALDH1A1 in regulating spermatogenesis postnatally. ..
- Zhou L, Jiang Y, Yan T, Di G, Shen Z, Shao Z, et al. The prognostic role of cancer stem cells in breast cancer: a meta-analysis of published literatures. Breast Cancer Res Treat. 2010;122:795-801 pubmed publisher..001) were significantly associated with poor overall survival (OS). The stem cell markers are prognostic factors in breast cancer. Larger clinical studies are required to further evaluate the role of these markers in clinical practice. ..
- Ho K, Allali Hassani A, Hurley T, Weiner H. Differential effects of Mg2+ ions on the individual kinetic steps of human cytosolic and mitochondrial aldehyde dehydrogenases. Biochemistry. 2005;44:8022-9 pubmed..In contrast, the metal ions affected only the NAD(+) activation of ALDH1. This latter finding and other features described here can be rationalized on the basis of the known three-dimensional structures of the isozymes. ..
- Li X, Kakkad B, Ong D. Estrogen directly induces expression of retinoic acid biosynthetic enzymes, compartmentalized between the epithelium and underlying stromal cells in rat uterus. Endocrinology. 2004;145:4756-62 pubmed..A retinol dehydrogenase that we have previously described, eRolDH, and the retinal dehydrogenase, RalDH II, were found to have markedly increased uterine mRNA levels within 4 h of E2 administration, ..
- Gagnon I, Duester G, Bhat P. Kinetic analysis of mouse retinal dehydrogenase type-2 (RALDH2) for retinal substrates. Biochim Biophys Acta. 2002;1596:156-62 pubmedb>Retinal dehydrogenase (RALDH) isozymes catalyze the terminal oxidation of retinol into retinoic acid (RA) that is essential for embryogenesis and tissue differentiation...
- Niederreither K, Vermot J, Schuhbaur B, Chambon P, Dolle P. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Development. 2002;129:3563-74 pubmed..We suggest that RA signaling cooperates with a posteriorly restricted factor such as dHand, to generate a functional zone of polarizing activity (ZPA). ..
- Vermot J, Niederreither K, Garnier J, Chambon P, Dolle P. Decreased embryonic retinoic acid synthesis results in a DiGeorge syndrome phenotype in newborn mice. Proc Natl Acad Sci U S A. 2003;100:1763-8 pubmed
- Gavalas A. ArRAnging the hindbrain. Trends Neurosci. 2002;25:61-4 pubmed..Progressively higher RA signalling is necessary for assigning more posterior territories. Complete RA deficiency results in the caudal hindbrain assuming an r4-like identity, which is postulated to be the hindbrain ground state. ..
- Fan X, Molotkov A, Manabe S, Donmoyer C, Deltour L, Foglio M, et al. Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism of retinoic acid synthesis in the developing retina. Mol Cell Biol. 2003;23:4637-48 pubmed..Our findings suggest that RA signaling may be necessary only during early stages of retina development and that if RA synthesis is needed in dorsal retina, it is catalyzed by multiple enzymes, including Raldh1. ..
- Huq M, Tsai N, Gupta P, Wei L. Regulation of retinal dehydrogenases and retinoic acid synthesis by cholesterol metabolites. EMBO J. 2006;25:3203-13 pubmed..This study uncovered a novel crosstalk between cholesterol and RA biosynthesis. ..
- Park S, Lee H, Li H, Shipitsin M, Gelman R, Polyak K. Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res. 2010;16:876-87 pubmed publisher..Our findings suggest that in breast cancer, the frequency of tumor cells positive for stem cell-like and more differentiated cell markers varies according to tumor subtype and histologic stage. ..
- Charafe Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B, et al. Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res. 2010;16:45-55 pubmed publisher..ALDH1 expression represents the first independent prognostic marker to predict metastasis and poor patient outcome in IBC. The results illustrate how stem cell research can translate into clinical practice in the IBC field. ..
- Balicki D. Moving forward in human mammary stem cell biology and breast cancer prognostication using ALDH1. Cell Stem Cell. 2007;1:485-7 pubmed
- Blentic A, Gale E, Maden M. Retinoic acid signalling centres in the avian embryo identified by sites of expression of synthesising and catabolising enzymes. Dev Dyn. 2003;227:114-27 pubmed..This strategy provides a basis for understanding the phenotypes of retinoic acid teratology and retinoic acid-deficiency syndromes...
- Mic F, Molotkov A, Molotkova N, Duester G. Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation. Dev Dyn. 2004;231:270-7 pubmed..Our findings suggest that RA functions as one of the signals needed for invagination of the retina to generate an optic cup. ..
- Zhang J, Smith D, Yamamoto M, Ma L, McCaffery P. The meninges is a source of retinoic acid for the late-developing hindbrain. J Neurosci. 2003;23:7610-20 pubmed
- Kim M, Fleming J, Wang H, Abbruzzese J, Choi W, Kopetz S, et al. ALDH activity selectively defines an enhanced tumor-initiating cell population relative to CD133 expression in human pancreatic adenocarcinoma. PLoS ONE. 2011;6:e20636 pubmed publisher..We have thus identified a distinct population of TICs that should lead to identification of novel targets for pancreatic cancer therapy. ..
- Tanei T, Morimoto K, Shimazu K, Kim S, Tanji Y, Taguchi T, et al. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin Cancer Res. 2009;15:4234-41 pubmed publisher..ALDH1-positive thus seems to be a more significantly predictive marker than CD44(+)/CD24(-) for the identification of breast cancer stem cells in terms of resistance to chemotherapy. ..
- De Brot M, Rocha R, Soares F, Gobbi H. Prognostic impact of the cancer stem cell related markers ALDH1 and EZH2 in triple negative and basal-like breast cancers. Pathology. 2012;44:303-12 pubmed publisher..Tumour microenvironment should be considered when studying prognostic impact of CSCs in breast cancer. ..
- Niederreither K, Abu Abed S, Schuhbaur B, Petkovich M, Chambon P, Dolle P. Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development. Nat Genet. 2002;31:84-8 pubmed..We provide genetic evidence that ALDH1A2 and CYP26A1 activities concurrently establish local embryonic retinoic acid levels that must be finely tuned to allow posterior organ development and to prevent spina bifida. ..
- Heerma van Voss M, van der Groep P, Bart J, van der Wall E, van Diest P. Expression of the stem cell marker ALDH1 in BRCA1 related breast cancer. Cell Oncol (Dordr). 2011;34:3-10 pubmed publisher..Besides, (peritumoral) stromal ALDH1 expression was also more frequent in BRCA1 mutation carriers. ALDH1 may therefore be a diagnostic marker and a therapeutic target of BRCA1 related breast cancer. ..
- Wang Y, Yo Y, Lee H, Liao Y, Chao T, Su P, et al. ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome. Am J Pathol. 2012;180:1159-69 pubmed publisher..The use of a combination of ALDH1 with other stem cell markers may help define ovarian cancer stem cells more stringently. ..
- Feng L, Hernandez R, Waxman J, Yelon D, Moens C. Dhrs3a regulates retinoic acid biosynthesis through a feedback inhibition mechanism. Dev Biol. 2010;338:1-14 pubmed publisher..Dhrs3a is thus an RA-induced feedback inhibitor of RA biosynthesis. We conclude that retinaldehyde availability is an important level at which RA biosynthesis is regulated in vertebrate embryos. ..
- Chute J, Muramoto G, Whitesides J, Colvin M, Safi R, Chao N, et al. Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci U S A. 2006;103:11707-12 pubmed..Modulation of ALDH activity and retinoid signaling is a previously unrecognized and effective strategy to amplify human HSCs...
- Theodoropoulos P, Polioudaki H, Agelaki S, Kallergi G, Saridaki Z, Mavroudis D, et al. Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett. 2010;288:99-106 pubmed publisher..7% of the CTCs analyzed in seven patients, were ALDH1(high)/CD24(-/low). In conclusion, we report the existence of a subpopulation of CTCs with putative stem cell progenitor phenotypes in patients with metastatic breast cancer. ..
- Ozbek E, Calik G, Otunctemur A, Aliskan T, Cakir S, Dursun M, et al. Stem cell markers aldehyde dehydrogenase type 1 and nestin expressions in renal cell cancer. Arch Ital Urol Androl. 2012;84:7-11 pubmed..There is a need to perform more studies about stem cell markers in RCC with more patients and in these future studies lymph node metastasis, distant organ metastasis and survival rates should be included. ..
- Chen Y, Chen Y, Hsu H, Tseng L, Huang P, Lu K, et al. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem Biophys Res Commun. 2009;385:307-13 pubmed publisher..In summary, it is likely that ALDH1 is a specific marker for the cancer stem-like cells of HNSCC. ..
- Morimoto K, Kim S, Tanei T, Shimazu K, Tanji Y, Taguchi T, et al. Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression. Cancer Sci. 2009;100:1062-8 pubmed publisher..Breast cancers with ALDH1+ cancer stem cells posses biologically aggressive phenotypes that tend to have a poor prognosis, and ALDH1+ cancer stem cells are characterized by ER-, Ki67-, and HER2+. ..
- Wakamatsu Y, Sakamoto N, Oo H, Naito Y, Uraoka N, Anami K, et al. Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int. 2012;62:112-9 pubmed publisher..001). These results indicate that these CSC markers are important in tumor invasion and metastasis and may be good markers indicating long-term survival in patients with GC. ..
- Vogler T, Kriegl L, Horst D, Engel J, Sagebiel S, Schäffauer A, et al. The expression pattern of aldehyde dehydrogenase 1 (ALDH1) is an independent prognostic marker for low survival in colorectal tumors. Exp Mol Pathol. 2012;92:111-7 pubmed publisher..This correlation was found univariately and when applying the multivariate Cox-model. ALDH1 expression pattern is an independent prognostic marker for survival of T3 N0 M0 G2 colorectal cancer patients. ..
- Madjd Z, Ramezani B, Molanae S, Asadi Lari M. High expression of stem cell marker ALDH1 is associated with reduced BRCA1 in invasive breast carcinomas. Asian Pac J Cancer Prev. 2012;13:2973-8 pubmed..Therefore, ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate. ..
- Stock A, Booth S, Cerundolo V. Prostaglandin E2 suppresses the differentiation of retinoic acid-producing dendritic cells in mice and humans. J Exp Med. 2011;208:761-73 pubmed publisher..Given the role of PGE2 in regulating the development of RA-producing DCs, modulating this pathway may prove a novel means to control the development of gut-tropic immune responses. ..
- Raimondi C, Gradilone A, Naso G, Vincenzi B, Petracca A, Nicolazzo C, et al. Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Res Treat. 2011;130:449-55 pubmed publisher..The detection of cells in mesenchymal transition, retaining EMT and stemness features, may contribute to discover additional therapeutic targets useful to eradicate micrometastatic disease in breast cancer. ..
- Dontu G. Breast cancer stem cell markers - the rocky road to clinical applications. Breast Cancer Res. 2008;10:110 pubmed publisher..These very interesting findings caution that the success of our efforts in translating cancer stem cell research into clinical practice depends on how thorough and rigorous we are at characterizing these cells. ..
- Wagner E, Luo T, DRAGER U. Retinoic acid synthesis in the postnatal mouse brain marks distinct developmental stages and functional systems. Cereb Cortex. 2002;12:1244-53 pubmed..The transient cortical expression points to a brief RA-critical period during differentiation of the cortical network that serves in the coordination of sensory-motor activity with emotional and recently learned information. ..
- Gong C, Yao H, Liu Q, Chen J, Shi J, Su F, et al. Markers of tumor-initiating cells predict chemoresistance in breast cancer. PLoS ONE. 2010;5:e15630 pubmed publisher..It highlights the importance of targeting T-ICs, rather than eliminating the bulk of rapidly dividing and terminally differentiated cells, in novel anti-cancer strategies. ..
- Corcoran J, So P, Maden M. Disruption of the retinoid signalling pathway causes a deposition of amyloid beta in the adult rat brain. Eur J Neurosci. 2004;20:896-902 pubmed..This suggests that retinoids are important for the maintenance of the adult nervous system and their loss may in part play a role in Alzheimer's disease. ..
- Fujiwara K, Kikuchi M, Horiguchi K, Kusumoto K, Kouki T, Kawanishi K, et al. Estrogen receptor alpha regulates retinaldehyde dehydrogenase 1 expression in rat anterior pituitary cells. Endocr J. 2009;56:963-73 pubmed..These results strongly suggest that RALDH1 mRNA expression is suppressed by 17beta-estradiol through ERalpha, and that estrogen regulates the expression of RALDH1 and production of RA in the anterior pituitary gland. ..
- Mic F, Haselbeck R, Cuenca A, Duester G. Novel retinoic acid generating activities in the neural tube and heart identified by conditional rescue of Raldh2 null mutant mice. Development. 2002;129:2271-82 pubmed
- Yu M, Yu P, Leghari I, Ge C, Mi Y, Zhang C. RALDH2, the enzyme for retinoic acid synthesis, mediates meiosis initiation in germ cells of the female embryonic chickens. Amino Acids. 2013;44:405-12 pubmed publisher..Altogether, these studies indicate that RA synthesis by the enzyme RALDH2 and signaling through its receptor is crucial for meiosis initiation in chicken embryonic ovary...
- Sládek N, Kollander R, Sreerama L, Kiang D. Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study. Rational individualization of oxazaphosphorine-based cancer chemot. Cancer Chemother Pharmacol. 2002;49:309-21 pubmed..However, ALDH3A1 levels in certain other malignancies, e.g. those of the alimentary tract and lung, may be of a sufficient magnitude in that regard. ..
- Niederreither K, Fraulob V, Garnier J, Chambon P, Dolle P. Differential expression of retinoic acid-synthesizing (RALDH) enzymes during fetal development and organ differentiation in the mouse. Mech Dev. 2002;110:165-71 pubmed..Only Raldh1 expression is seen after birth in specific brain structures. These data indicate a requirement for regulated RA synthesis in various differentiating organs. ..
- Sakakibara M, Fujimori T, Miyoshi T, Nagashima T, Fujimoto H, Suzuki H, et al. Aldehyde dehydrogenase 1-positive cells in axillary lymph node metastases after chemotherapy as a prognostic factor in patients with lymph node-positive breast cancer. Cancer. 2012;118:3899-910 pubmed publisher..The authors concluded that ALDH1-positive status may represent a surrogate marker as a new concept in patients with lymph node-positive breast cancer. ..
- Fan X, Ouyang N, Teng H, Yao H. Isolation and characterization of spheroid cells from the HT29 colon cancer cell line. Int J Colorectal Dis. 2011;26:1279-85 pubmed publisher..Spheroid cell models also enable the study of colon cancer chemoresistance and metastasis and may help to elucidate the role of cancer stem cells in colon cancer. ..
- Reichert B, Yasmeen R, Jeyakumar S, Yang F, Thomou T, Alder H, et al. Concerted action of aldehyde dehydrogenases influences depot-specific fat formation. Mol Endocrinol. 2011;25:799-809 pubmed publisher..Our data suggest a paradigm for regulation of fat depots through the concerted action of Aldh1 enzymes that establish RA-dependent tandem regulation of transcription factors ZFP423 and PPAR? in a depot-specific manner. ..
- Mey J, Babiuk R, Clugston R, Zhang W, Greer J. Retinal dehydrogenase-2 is inhibited by compounds that induce congenital diaphragmatic hernias in rodents. Am J Pathol. 2003;162:673-9 pubmed..Specifically, inhibition of retinal dehydrogenase-2 (RALDH2), a key enzyme necessary for the production of retinoic acid and that is expressed in the ..
- Nalwoga H, Arnes J, Wabinga H, Akslen L. Expression of aldehyde dehydrogenase 1 (ALDH1) is associated with basal-like markers and features of aggressive tumours in African breast cancer. Br J Cancer. 2010;102:369-75 pubmed publisher..Studies are required to elucidate the importance of these findings for improved understanding of breast cancer biology. ..
- Molotkov A, Duester G. Genetic evidence that retinaldehyde dehydrogenase Raldh1 (Aldh1a1) functions downstream of alcohol dehydrogenase Adh1 in metabolism of retinol to retinoic acid. J Biol Chem. 2003;278:36085-90 pubmed..These observations demonstrate that Raldh1 functions downstream of Adh1 in the oxidative metabolism of excess retinol and that toxicity correlates primarily with accumulating retinol rather than retinaldehyde. ..
- Wang Y, Zhe H, Gao P, Zhang N, Li G, Qin J. Cancer stem cell marker ALDH1 expression is associated with lymph node metastasis and poor survival in esophageal squamous cell carcinoma: a study from high incidence area of northern China. Dis Esophagus. 2012;25:560-5 pubmed publisher..The expression of ALDH1 protein in nucleus of the ESCC is significantly associated with lymph node metastasis and poor survival. Our results highly indicate the involvement of ALDH1 in the aggressive behavior of ESCC. ..
- Molenaar R, Knippenberg M, Goverse G, Olivier B, de Vos A, O Toole T, et al. Expression of retinaldehyde dehydrogenase enzymes in mucosal dendritic cells and gut-draining lymph node stromal cells is controlled by dietary vitamin A. J Immunol. 2011;186:1934-42 pubmed publisher..Our results show that RA-dependent signaling within the intestine is indispensable for RALDH activity in the draining MLN. ..
- Alsop D, Matsumoto J, Brown S, Van der Kraak G. Retinoid requirements in the reproduction of zebrafish. Gen Comp Endocrinol. 2008;156:51-62 pubmed