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Current Stem Cell Research & Therapy


ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

ALDH as a Stem Cell Marker in Solid Tumors

Author(s): Mariel E. Toledo-Guzmán, Miguel Ibañez Hernández, Ángel A. Gómez-Gallegos and Elizabeth Ortiz-Sánchez*

Volume 14, Issue 5, 2019

Page: [375 - 388] Pages: 14

DOI: 10.2174/1574888X13666180810120012

Price: $65


Aldehyde dehydrogenase (ALDH) is an enzyme that participates in important cellular mechanisms as aldehyde detoxification and retinoic acid synthesis; moreover, ALDH activity is involved in drug resistance, a characteristic of cancer stem cells (CSCs). Even though ALDH is found in stem cells, CSCs and progenitor cells, this enzyme has been successfully used to identify and isolate cell populations with CSC properties from several tumor origins.

ALDH is allegedly involved in cell differentiation through its product, retinoic acid. However, direct or indirect ALDH inhibition, using specific inhibitors or retinoic acid, has shown a reduction in ALDH activity, along with the loss of stem cell traits, reduction of cell proliferation, invasion, and drug sensitization. For these reasons, ALDH and retinoic acid are promising therapeutic targets.

This review summarizes the current evidence for ALDH as a CSCs marker in solid tumors, as well as current knowledge about the functional roles of ALDH in CSCs. We discuss the controversy of ALDH activity to maintain CSC stemness, or conversely, to promote cell differentiation. Finally, we review the advances in using ALDH inhibitors as anti-cancer drugs.

Keywords: Aldehyde dehydrogenase, cancer stem cell, retinoic acid, all-trans-retinoic acid, stemness, isozyme.

Black WJ, Stagos D, Marchitti SA, et al. Human aldehyde dehydrogenase genes: Alternatively-spliced transcriptional variants and their suggested nomenclature. Pharmacogenet Genomics 2009; 19(11): 893-902.
Vasiliou V, Pappa A, Estey T. Role of human aldehyde dehydrogenases in endobiotic and xenobiotic metabolism. Drug Metab Rev 2004; 36(2): 279-99.
Sládek NE. Human aldehyde dehydrogenases: Potential pathological, pharmacological, and toxicological impact. J Biochem Mol Toxicol 2003; 17(1): 7-23.
Lindahl R. Aldehyde dehydrogenases and their role in carcinogenesis. Crit Rev Biochem Mol Biol 1992; 27(4-5): 283-335.
Chen CH, Sun L, Mochly-Rosen D. Mitochondrial aldehyde dehydrogenase and cardiac diseases. Cardiovasc Res 2010; 88(1): 51-7.
Jackson B, Brocker C, Thompson DC, et al. Update on the aldehyde dehydrogenase gene [ALDH] superfamily. Hum Genomics 2011; 5(4): 283-303.
Marchiti SA, Brocker C, Stagos D, Vasiliou V. Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Metab Toxicol 2008; 4(6): 697-720.
Vasiliou V, Thompson DC, Smith C, Fujita M, Chen Y. Aldehyde dehydrogenases: From eye crystallins to metabolic disease and cancer stem cells. Chem Biol Interact 2013; 202(1-3): 2-10.
Piatigorsky J. Review: A case for corneal crystallins. J Ocul Pharmacol Ther 2000; 16(2): 173-80.
Marchitti SA, Chen Y, Thompson DC, Vasiliou V. Ultraviolet radiation: Cellular antioxidant response and the role of ocular aldehyde dehydrogenase enzymes. Eye Contact Lens 2011; 37(4): 206-13.
Jester JV, Budge A, Fisher S, Huang J. Corneal keratocytes: Phenotypic and species differences in abundant protein expression and in vitro light-scattering. Invest Ophthalmol Vis Sci 2005; 46(7): 2369-78.
Pappa A, Sophos NA, Vasiliou V. Corneal and stomach expression of aldehyde dehydrogenases: From fish to mammals. Chem Biol Interact 2001; 130-132: 181-91.
Dollé L, Boulter L, Leclercq IA, van Grunsven LA. Next generation of ALDH substrates and their potential to study maturational lineage biology in stem and progenitor cells. Am J Physiol Gastrointest Liver Physiol 2015; 308(7): G573-8.
Singh S, Brocker C, Koppaka V, et al. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. Free Radic Biol Med 2013; 56: 89-101.
Lassen N, Bateman JB, Estey T, et al. Multiple and additive functions of ALDH3A1 and ALDH1A1: Cataract phenotype and ocular oxidative damage in Aldh3a1[-/-]/Aldh1a1[-/-] knock-out mice. J Biol Chem 2007; 282(35): 25668-76.
Muzio G, Maggiora M, Paiuzzi E, Oraldi M, Canuto RA. Aldehyde dehydrogenases and cell proliferation. Free Radic Biol Med 2012; 52(4): 735-46.
Grünblatt E, Riederer P. Aldehyde dehydrogenase [ALDH] in Alzheimer’s and Parkinson’s disease. J Neural Transm 2016; 123(2): 83-90.
Casida JE, Ford B, Jinsmaa Y, Sullivan P, Cooney A, Goldstein DS. Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of parkinsons disease. Chem Res Toxicol 2014; 27(8): 1359-61.
Sladek NE. Leukemic cell insensitivity to cyclophosphamide and other oxazaphosphorines mediated by aldehyde dehydrogenase.[s]. Cancer Treat Res 2002; 112: 161-75.
Moreb J. Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther 2008; 3(4): 237-46.
Becker AJ. MA and TE. Cytological demostration of the clonal nature of spleen colonies derived fom transplanted mouse marrow cells. Nature 1963; 197: 452-4.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414(6859): 105-11.
Tang DG. Understanding cancer stem cell heterogeneity and plasticity. Cell Res 2012; 22(3): 457-72.
Hess D a, Wirthlin L, Craft TP, et al.Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem. Blood 2006; 107(5): 2162-9.
Fallon P, Gentry T, Balber AE, et al. Mobilized peripheral blood SSC lo ALDH br cells have the phenotypic and functional properties of primitive haematopoietic cells and their number correlates with engraftment following autologous transplantation. Br J Haematol 2003; 122(1): 99-108.
Bhatia M, Wang JC, Kapp U, Bonnet D, Dick JE. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci USA 1997; 94(10): 5320-5.
Bhatia M, Bonnet D, Murdoch B, Gan OI, Dick JE. A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat Med 1998; 4(9): 1038-45.
Dao MA, Arevalo J, Nolta JA. Reversibility of CD34 expression on human hematopoietic stem cells that retain the capacity for secondary reconstitution. Blood 2003; 101(1): 112-8.
Keller LH. Bone marrow-derived aldehyde dehydrogenase-bright stem and progenitor cells for ischemic repair. Congest Heart Fail 2009; 15(4): 202-6.
Jones RJ, Barber JP, Vala MS, et al. Assessment of aldehyde dehydrogenase in viable cells. Blood 1995; 85(10): 2742-6.
Storms RW, Trujillo AP, Springer JB, et al. Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci USA 1999; 96(16): 9118-23.
Kastan BMB, Schlaffer E, Russo J, Colvin M, Civin C, Hilton J. Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells. Blood J 1990; 75(10): 1947-50.
Pearce DJ, Taussig D, Simpson C, et al. Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples. Stem Cells 2005; 23(6): 752-60.
Christ O, Lucke K, Imren S, et al. Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity. Haematologica 2007; 92(90): 1165-72.
Marcato P, Dean CA, Giacomantonio CA, Lee PWK. Aldehyde dehydrogenase its role as a cancer stem cell marker comes down to the specific isoform. Cell Cycle 2011; 10(9): 1378-84.
Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev 2011; 7(2): 292-306.
Martignani E, Eirew P, Accornero P, Eaves CJ, Baratta M. Human milk protein production in xenografts of genetically engineered bovine mammary epithelial stem cells. PLoS One 2010; 5(10)e13372
Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007; 1(5): 555-67.
Huang EH, Hynes MJ, Zhang T, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells [sc] and tracks sc overpopulation during colon tumorigenesis. Cancer Res 2009; 69(8): 3382-9.
Obermair FJ, Fiorelli R, Schroeter A, et al. A novel classification of quiescent and transit amplifying adult neural stem cells by surface and metabolic markers permits a defined simultaneous isolation. Stem Cell Res 2010; 5(2): 131-43.
Burger PE, Gupta R, Xiong X, et al. High ALDH activity: A novel functional marker of murine prostate stem/progenitor cells. Stem Cells 2009; 27(9): 2220-8.
Vlashi E, Pajonk F. Cancer stem cells, cancer cell plasticity and radiation therapy. Semin Cancer Biol 2015; 31: 28-35.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983-8.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414(6859): 105-11.
Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells - Perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res 2006; 66(19): 9339-44.
Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367(6464): 645-8.
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3(7): 730-7.
Visvader JE, Lindeman GJ. Cancer stem cells: Current status and evolving complexities. Cell Stem Cell 2012; 10(6): 717-28.
Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells - Old concepts, new insights. Cell Death Differ 2008; 15(6): 947-58.
Medema JP. Cancer stem cells: The challenges ahead. Nat Cell Biol 2013; 15(4): 338-44.
Shackleton M, Quintana E, Fearon ER, Morrison SJ. Heterogeneity in cancer: Cancer stem cells versus clonal evolution. Cell 2009; 138(5): 822-9.
Visvader JE. Cells of origin in cancer. Nature 2011; 469(7330): 314-22.
Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003; 3(12): 895-902.
Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A. Tumor growth need not be driven by rare cancer stem cells. Science 2007; 317(5836): 337.
Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63(18): 5821-8.
Zhou B-BS, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumour-initiating cells: Challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 2009; 8(10): 806-23.
Hill RP. Identifying cancer stem cells in solid tumors: Case not proven. Cancer Res 2006; 66(4): 1891-5.
Atkinson RL, Yang WT, Rosen DG, et al. Cancer stem cell markers are enriched in normal tissue adjacent to triple negative breast cancer and inversely correlated with DNA repair deficiency. Breast Cancer Res 2013; 15(5): R77.
Hoang VT, Buss EC, Wang W, et al. The rarity of ALDH+cells is the key to separation of normal versus leukemia stem cells by ALDH activity in AML patients. Int J Cancer 2015; 137(3): 525-36.
Blume R, Rempel E, Manta L, et al. The molecular signature of AML with increased ALDH activity suggests a stem cell origin. Leuk Lymphoma 2018; 59(9): 2201-10.
Ajani JA, Song S, Hochster HS, Steinberg IB. Cancer stem cells: The promise and the potential. Semin Oncol 2015; 42(S1): S3-S17.
Chen Y, Orlicky D, Matsumoto A, Singh S, Thompson D, Vasiliou V. Aldehyde dehydrogenase 1B1 [ALDH1B1] is a potential biomarker for human colon cancer. Biochem Biophys Res Commun 2011; 405(2): 173-9.
Condello S, Morgan CA, Nagdas S, et al. β-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids. Oncogene 2015; 34(18): 2297-308.
Meng E, Mitra A, Tripathi K, et al. ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and dna repair network signaling. PLoS One 2014; 9(9)e107142
Gao F, Zhou B, Xu J, et al. The role of LGR5 and ALDH1A1 in non-small cell lung cancer: Cancer progression and prognosis. Biochem Biophys Res Commun 2015; 462(2): 91-8.
Ma Y, Li M, Si J, et al. Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1 and CD44 via autophagy in non-small lung cancer. Int J Oncol 2016; 48(6): 2349-58.
Liu Y, Baglia M, Zheng Y, et al. ALDH1A1 mRNA expression in association with prognosis of triple-negative breast cancer. Oncotarget 2015; 6(38): 41360-9.
Sun M, Zhao H, Xiao Q, et al. Combined expression of aldehyde dehydrogenase 1A1 and β -catenin is associated with lymph node metastasis and poor survival in breast cancer patients following cyclophosphamide treatment. Oncol Rep 2015; 34(6): 3163-73.
Wang W, Li Y, Liu N, Gao Y, Li L. MiR-23b controls ALDH1A1 expression in cervical cancer stem cells. BMC Cancer 2017; 17(1): 292.
Tanaka K, Tomita H, Hisamatsu K, et al. ALDH1A1-overexpressing cells are differentiated cells but not cancer stem or progenitor cells in human hepatocellular carcinoma. Oncotarget 2015; 6(28): 24722-32.
Yan Z, Xu L, Zhang J, et al. Biochemical and Biophysical Research Communications Aldehyde dehydrogenase 1A1 stabilizes transcription factor Gli2 and enhances the activity of Hedgehog signaling in hepatocellular cancer. Biochem Biophys Res Commun 2016; 471(4): 466-73.
Wang Y, Shao F, Chen L. ALDH1A2 suppresses epithelial ovarian cancer cell proliferation and migration by downregulating. OncoTargets Ther 2018; 11: 599-608.
Kim H, Lapointe J, Kaygusuz G, et al. The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer. Cancer Res 2005; 65(18): 8118-24.
Kawasoe M, Yamamoto Y, Okawa K, et al. Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2. Exp Hematol 2013; 41(7): 597-603.
Pérez-Alea M, McGrail K, Sánchez-Redondo S, et al. ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment. Oncogene 2017; 36(O41): 5695-708.
Thomas ML, de Antueno R, Coyle KM, et al. Citral reduces breast tumor growth by inhibiting the cancer stem cell marker ALDH1A3. Mol Oncol 2016; 10(9): 1485-96.
Shao C, Sullivan JP, Girard L. Essential role of aldehyde dehydrogenase 1A3 [ALDH1A3] for the maintenance of non-small cell lung cancer stem cells is associated with the STAT3 pathway. Clin Cancer Res 2014; 20(15): 4154-66.
Golubovskaya V, Brien SO, Ho B, et al. Down - regulation of ALDH1A3, CD44 or MDR1 sensitizes resistant cancer cells to FAK autophosphorylation inhibitor Y15. J Cancer Res Clin Oncol 2015; 141(9): 1613-31.
Feng H, Liu Y, Bian X, Zhou F, Liu Y. ALDH1A3 affects colon cancer in vitro proliferation and invasion depending on CXCR4 status. Br J Cancer 2018; 118(2): 224-32.
Singh S, Arcaroli J, Chen Y, et al. ALDH1B1 is crucial for colon tumorigenesis by modulating wnt / β -Catenin, Notch and PI3K / Akt signaling pathways. PLoS One 2015; 10(5)e0121648
Wang X, Yu Y, He Y, et al. Upregulation of ALDH1B1 promotes tumor progression in osteosarcoma. Oncotarget 2017; 9(2): 2502-14.
Singh S, Arcaroli JJ, Orlicky DJ, et al. ALDH1B1 as a modulator of pancreatic adenocarcinoma. Pancreas 2016; 45(1): 117-22.
Matsumoto A, Arcaroli J, Chen Y, et al. Aldehyde dehydrogenase 1B1 : A novel immunohistological marker for colorectal cancer. Br J Cancer 2017; 117(10): 1537-43.
Qiu Y, Pu T, Guo P, et al. ALDH+/CD44+cells in breast cancer are associated with worse prognosis and poor clinical outcome. Exp Mol Pathol 2016; 100(1): 145-50.
Sullivan JP, Spinola M, Dodge M, et al. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on Notch signaling. Cancer Res 2010; 70(23): 9937-48.
Zhang Q, Lu C, Fang T, et al. Notch3 functions as a regulator of cell self-renewal by interacting with the β-catenin pathway in hepatocellular carcinoma. Oncotarget 2015; 6(6): 3669-79.
Zhao D, Mo Y, Li M, et al. NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer stem cells. J Clin Invest 2014; 124(12): 5453-65.
Ying M, Wang S, Sang Y, et al. Regulation of glioblastoma stem cells by retinoic acid: Role for Notch pathway inhibition. Oncogene 2011; 30(31): 3454-67.
Young MJ, Wu YH, Chiu WT, et al. All-trans retinoic acid downregulates ALDH1-mediated stemness and inhibits tumour formation in ovarian cancer cells. Carcinogenesis 2015; 36(4): 498-507.
Clark DW, Palle K. Aldehyde dehydrogenases in cancer stem cells: Potential as therapeutic targets. Ann Transl Med 2016; 4(24): 518-8.
Xu X, Chai S, Wang P, et al. Aldehyde dehydrogenases and cancer stem cells. Cancer Lett 2015; 369(1): 50-7.
Masetti R, Biagi C, Zama D, et al. Retinoids in pediatric onco-hematology: The model of acute promyelocytic leukemia and neuroblastoma. Adv Ther 2012; 29(9): 747-62.
Siddikuzzaman Guruvayoorappan C. Berlin Grace VM. All trans retinoic acid and cancer. Immunopharmacol Immunotoxicol 2011; 33(2): 241-9.
Theodosiou M, Laudet V, Schubert M. From carrot to clinic: An overview of the retinoic acid signaling pathway. Cell Mol Life Sci 2010; 67(9): 1423-45.
Niles R. Recent advances in the use of vitamin A [retinoids] in the prevention and treatment of cancer. Nutrition 2000; 16(11-12): 1084-9.
Zhao D, McCaffery P, Ivins KJ, et al. Molecular identification of a major retinoic-acid-synthesizing enzyme, a retinaldehyde-specific dehydrogenase. Eur J Biochem 1996; 240(1): 15-22.
Duester G, Mic FA, Molotkov A. Cytosolic retinoid dehydrogenases govern ubiquitous metabolism of retinol to retinaldehyde followed by tissue-specific metabolism to retinoic acid. Chem Biol Interact 2003; 143-144: 201-10.
Das BC, Thapa P, Karki R, et al. Retinoic acid signaling pathways in development and diseases. Bioorg Med Chem 2014; 22(2): 673-83.
Gudas LJ, Wagner JA. Retinoids regulate stem cell differentiation. J Cell Physiol 2011; 226(2): 322-30.
Ginestier C, Wicinski J, Cervera N, et al. Retinoid signaling regulates breast cancer stem cell differentiation. Cell Cycle 2009; 8(20): 3297-302.
Herreros-Villanueva M, Er T-K, Bujanda L. Retinoic acid reduces stem cell-like features in pancreatic cancer cells. Pancreas 2015; 44(6): 918-24.
Stavridis MP, Collins BJ, Storey KG. Retinoic acid orchestrates fibroblast growth factor signalling to drive embryonic stem cell differentiation. Development 2010; 137(6): 881-90.
Engberg N, Kahn M, Petersen DR, Hansson M, Serup P. Retinoic acid synthesis promotes development of neural progenitors from mouse embryonic stem cells by suppressing endogenous, Wnt-dependent nodal signaling. Stem Cells 2010; 28(9): 1498-509.
Yu Z, Wu S, Liu Z, et al. Sonic hedgehog and retinoic acid induce bone marrow-derived stem cells to differentiate into glutamatergic neural cells. J Immunoassay Immunochem 2015; 36(1): 1-15.
Reynolds CP. Differentiating agents in pediatric malignancies: Retinoids in neuroblastoma. Curr Oncol Rep 2000; 2(6): 511-8.
Petrie K, Zelent A, Waxman S. Differentiation therapy of acute myeloid leukemia: Past, present and future. Curr Opin Hematol 2009; 16(2): 84-91.
Elizondo G, Corchero J, Sterneck E, Gonzalez FJ. Feedback inhibition of the retinaldehyde dehydrogenase gene ALDH1 by retinoic acid through retinoic acid receptor α and CCAAT/enhancer-binding protein β. J Biol Chem 2000; 275(50): 39747-53.
Lim YC, Kang HJ, Kim YS, Choi EC. All-trans-retinoic acid inhibits growth of head and neck cancer stem cells by suppression of Wnt/β-catenin pathway. Eur J Cancer 2012; 48(17): 3310-8.
Froeling FEM, Feig C, Chelala C, et al. Retinoic acid-induced pancreatic stellate cell quiescence reduces paracrine Wntβ-catenin signaling to slow tumor progression. Gastroenterology 2011; 141(4): 1486-97.
Moreb JS, Ucar-Bilyeu DA, Khan A. Use of retinoic acid/aldehyde dehydrogenase pathway as potential targeted therapy against cancer stem cells. Cancer Chemother Pharmacol 2017; 79(2): 295-301.
Deng S, Yang X, Lassus H, et al. Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 [ALDH1], in human epithelial cancers. PLoS One 2010; 5(4)e10277
Rao Q, Yao T, Zhang B, et al. Expression and functional role of ALDH1 in cervical carcinoma cells. Asian Pac J Cancer Prev 2012; 13(4): 1325-31.
Landen CNJ, Goodman B, Katre AA, et al. Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther 2010; 9(12): 3186-99.
Shimamura M, Kurashige T, Mitsutake N, Nagayama Y. Aldehyde dehydrogenase activity plays no functional role in stem cell-like properties in anaplastic thyroid cancer cell lines. Endocrine 2017; 55(3): 934-43.
Cojoc M, Peitzsch C, Kurth I, et al. Aldehyde dehydrogenase is regulated by β-Catenin/TCF and promotes radioresistance in prostate cancer progenitor cells. Cancer Res 2015; 75(7): 1482-94.
Mizuno T, Suzuki N, Makino H, et al. Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species. Gynecol Oncol 2015; 137(2): 299-305.
Januchowski R, Wojtowicz K, Zabel M. The role of aldehyde dehydrogenase [ALDH] in cancer drug resistance. Biomed Pharmacother 2013; 67(7): 669-80.
Zhao J. Cancer stem cells and chemoresistance: The smartest survives the raid. Pharmacol Ther 2016; 160: 145-58.
Moreb JS, Ucar D, Han S, et al. The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 [ALDH1A2 and ALDH2] is detected by ALDEFLUOR, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance. Chem Biol Interact 2012; 195(1): 52-60.
Croker AK, Allan AL. Inhibition of aldehyde dehydrogenase [ALDH] activity reduces chemotherapy and radiation resistance of stem-like ALDHhiCD44+ human breast cancer cells. Breast Cancer Res Treat 2012; 133(1): 75-87.
Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 2008; 10(2): R25.
Moreb JS, Maccow C, Schweder M, Hecomovich J. Expression of antisense RNA to aldehyde dehydrogenase Class-1 sensitizes tumor cells to 4-Hydroperoxycyclophosphamide In vitro. J Pharmacol Exp Ther 2000; 293(2): 390-6.
Moreb JS, Muhoczy D, Ostmark B, Zucali JR. RNAi-mediated knockdown of aldehyde dehydrogenase class-1A1 and class-3A1 is specific and reveals that each contributes equally to the resistance against 4-hydroperoxycyclophosphamide. Cancer Chemother Pharmacol 2007; 59(1): 127-36.
Moreb JS, Gabr A, Vartikar GR, Gowda S, Zucali JR. Retinoic acid down-regulates aldehyde dehydrogenase and increases cytotoxicity of 4-hydroperoxycyclophosphamide and acetaldehyde. J Pharmacol Exp Ther 2005; 312(1): 339-45.
Koppaka V, Thompson DC, Chen Y, et al. Aldehyde dehydrogenase inhibitors: A comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application. Pharmacol Rev 2012; 64(3): 520-39.
Jiao Y, Hannafon BN, Ding W. Disulfiram’s anticancer activity : Evidences and mechanisms. Anticancer Agents Med Chem 2016; 16: 1378-84.
James MI, Iwuji C, Irving G, et al. Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett 2015; 364(2): 135-41.
Geng S, Alexandrou A, Li J. Breast cancer stem cells: Multiple Capacities in tumor metastasis. Cancer Lett 2014; 349(1): 1-7.
Kang Y, Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003; 3(6): 537-49.
Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007; 449(7163): 682-8.
Tomita H, Tanaka K, Tanaka T, Hara A. Aldehyde dehydrogenase 1A1 in stem cells and cancer. Oncotarget 2016; 7(10): 11018-32.
Croker AK, Goodale D, Chu J, et al. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med 2009; 13(8B): 2236-52.
Tanei T, Morimoto K, Shimazu K, 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(12): 4234-41.
Charafe-Jauffret E, Ginestier C, Iovino F, et al. ALDH1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res 2010; 16(1): 45-55.
Neumeister V, Agarwal S, Bordeaux J, Camp RL, Rimm DL. In situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, and cytokeratin identifies breast cancer patients with poor prognosis. Am J Pathol 2010; 176(5): 2131-8.
Marcato P, Dean CA, Pan D, et al. Human placenta-derived adherent cells prevent bone loss, myeloma in bone. Stem Cells 2011; 29(1): 32-45.
Marcato P, Dean CA, Liu RZ, et al. Aldehyde dehydrogenase 1A3 influences breast cancer progression via differential retinoic acid signaling. Mol Oncol 2015; 9(1): 17-31.
Wang J, Li Z, White J, Zhang L. Lung cancer stem cells and implications for future therapeutics. Cell Biochem Biophys 2014; 69(3): 389-98.
Alamgeer M, Peacock CD, Matsui W, Ganju V, Watkins DN. Cancer stem cells in lung cancer: Evidence and controversies. Respirology 2013; 18(5): 757-64.
Corominas-faja B, Oliveras-ferraros C, Cuyàs E, et al. A novel mechanism of acquired resistance to erlotinib targetable with the natural polyphenol silibinin Stem cell-like ALDH bright cellular states in EGFR - mutant non-small cell lung cancer. Cell Cycle 2013; 12(21): 3390-404.
Huang CP, Tsai MF, Chang TH, et al. ALDH-positive lung cancer stem cells confer resistance to epidermal growth factor receptor tyrosine kinase inhibitors. Cancer Lett 2013; 328(1): 144-51.
Liu J, Xiao Z, Wong SK-M, et al. Lung cancer tumorigenicity and drug resistance are maintained through ALDH hi CD44 hi tumor initiating cells. Oncotarget 2013; 4(10): 1698-711.
Li Z, Xiang Y, Xiang L, Xiao Y, Li F, Hao P. ALDH maintains the stemness of lung adenoma stem cells by suppressing the notch/CDK2/CCNE pathway. PLoS One 2014; 9(3)e92669
Miller JW, Hanson V, Johnson GD, Royalty JE, Richardson LC. From cancer screening to treatment: Service delivery and referral in the national breast and cervical cancer early detection program. Cancer 2014; 120(Suppl. 16): 2549-56.
Yao T, Chen Q, Zhang B, Zhou H, Lin Z. The expression of ALDH1 in cervical carcinoma. Med Sci Monit 2011; 17(8): HY21-6.
Liu S, Zheng P. High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer. Oncotarget 2013; 4(12): 2462-75.
Liu H, Wang H, Li C, et al. Spheres from cervical cancer cells display stemness and cancer drug resistance. Oncol Lett 2016; 12(3): 2184-8.
Ortiz-Sánchez E, Santiago-López L, Cruz-Domínguez VB, et al. Characterization of cervical cancer stem cell-like cells: phenotyping, stemness, and Human Papilloma Virus co-receptor expression. Oncotarget 2016; 7(22): 31943-54.
Lv Y, Yang L, Wang F, Wang F. Chemoradiation therapy reduces aldehyde dehydrogenase 1 expression in cervical cancer but does not improve patient survival. Med Oncol 2015; 32(5): 155.
Nguyen P, Giraud J, Staedel C, et al. All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth. Oncogene 2016; 35(43): 5619-28.
Zhi QM, Chen XH, Ji J, et al. Salinomycin can effectively kill ALDHhigh stem-like cells on gastric cancer. Biomed Pharmacother 2011; 65(7): 509-15.
Nishikawa S, Konno M, Hamabe A, et al. Aldehyde dehydrogenase high gastric cancer stem cells are resistant to chemotherapy. Int J Oncol 2013; 24(4): 1437-42.
Quintana E, Shackleton M, Foster HR, et al. Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer Cell 2010; 18(5): 510-23.
Prasmickaite L, Engesæter BØ, Skrbo N, et al. Aldehyde Dehydrogenase [ ALDH ] activity does not select for cells with enhanced aggressive properties in malignant melanoma. PLoS One 2010; 5(5)e10731
Boonyaratanakornkit JB, Yue L, Strachan LR, et al. Selection of tumorigenic melanoma cells using ALDH. J Invest Dermatol 2010; 130(12): 2799-808.
Luo Y, Dallaglio K, Chen Y, et al. ALDH1A isozymes are markers of human melanoma stem cells and potential therapeutic targets. Stem Cells 2012; 30(10): 2100-13.
Luo Y, Nguyen N, Fujita M. Isolation of human melanoma stem cells using ALDH as a marker. Curr Protoc Stem Cell Biol 2013; 20(26) Unit 3.8.
Yue L, Huang Z, Fong S, et al. Targeting ALDH1 to decrease tumorigenicity, growth and metastasis of human melanoma. Melanoma Res 2015; 25(2): 138-48.
Chen S, Huang E. The colon cancer stem cell microenvironment holds keys to future cancer therapy. J Gastrointest Surg 2014; 18(5): 1040-8.
Khorrami S, Hosseini AZ, Mowla SJ, Malekzadeh R. Verification of ALDH activity as a biomarker in colon cancer stem cells-derived HT-29 cell line. Iran J Cancer Prev 2015; 8(5)e3446
Shenoy A, Butterworth E, Huang EH. ALDH as a marker for enriching tumorigenic human colonic stem cells. Methods Mol Biol 2012; 916: 373-85.
Lin L, Fuchs J, Li C, Olson V, Bekaii-saab T, Lin J. STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH + / CD133 + stem cell-like human colon cancer cells. Biochem Biophys Res Commun 2011; 416(3-4): 246-51.
Jelski W, Zalewski B. The Activity of Class I, II, III, and IV Alcohol Dehydrogenase [ADH] Isoenzymes and Aldehyde Dehydrogenase [ALDH] in Liver Cancer. Dig Dis Sci 2008; 53(9): 2550-5.
Ma S, Chan KW, Lee TK, et al. Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res 2008; 6(7): 1146-53.

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