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Aldh1a1

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https://www.readbyqxmd.com/read/28537923/aldehyde-dehydrogenase-1a1-increases-nadh-levels-and-promotes-tumor-growth-via-glutathione-dihydrolipoic-acid-dependent-nad-reduction
#1
Baiyun Wang, Xue Chen, Zixi Wang, Wei Xiong, Tao Xu, Xinyuan Zhao, Yang Cao, Yanru Guo, Lin Li, She Chen, Song Huang, Xiaodong Wang, Min Fang, Zhirong Shen
Aldehyde dehydrogenase 1A1 (ALDH1A1) is a member of the aldehyde dehydrogenase superfamily that oxidizes aldehydes to their corresponding acids, reactions that are coupled to the reduction of NAD+ to NADH. We report here that ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH. The GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 is not affected by the aldehyde dehydrogenase inhibitor or by mutation of the residues in its aldehyde-binding pocket...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525556/transcriptome-of-the-gsh-depleted-lens-reveals-changes-in-detoxification-and-emt-signaling-genes-transport-systems-and-lipid-homeostasis
#2
Jeremy A Whitson, Xiang Zhang, Mario Medvedovic, Jenny Chen, Zongbo Wei, Vincent M Monnier, Xingjun Fan
Purpose: To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. Methods: The transcriptome of lens epithelia and fiber cells was obtained from C57BL/6 LEGSKO (lens GSH-synthesis knockout) and buthionine sulfoximine (BSO)-treated LEGSKO mice and compared to C57BL/6 wild-type mice using RNA-Seq. Transcriptomic data were confirmed by qPCR and Western blot/ELISA on a subset of genes...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28521404/silencing-tak1-alters-gene-expression-signatures-in-bladder-cancer-cells
#3
Jimin Chen, Nan Zhang, Jiaming Wen, Zhewei Zhang
The aim of the present study was to identify the differentially expressed genes (DEGs) that are induced by the silencing of transforming growth factor-β-activated kinase 1 (TAK1) in bladder cancer cells and to analyze the potential biological effects. Dataset GSE52452 from mutant fibroblast growth factor receptor 3 (FGFR3) bladder cancer cells transfected with control siRNA or TAK1-specific siRNA was downloaded from Gene Expression Omnibus. The DEGs between the two groups were identified using Limma package following data pre-processing by Affy in Bioconductor...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28512340/using-an-event-history-with-risk-free-model-to-study-the-genetics-of-alcoholism
#4
Hsin-Chou Yang, I-Chen Chen, Yuh-Chyuan Tsay, Zheng-Rong Li, Chun-Houh Chen, Hai-Gwo Hwu, Chen-Hsin Chen
Case-control genetic association studies typically ignore possible later disease onset in currently healthy subjects and assume that subjects with diseases equally contribute to the likelihood for inference, regardless of their onset age. Therefore, we used an event-history with risk-free model to simultaneously characterize alcoholism susceptibility and onset age in 65 independent non-Hispanic Caucasian males in the Collaborative Study on the Genetics of Alcoholism. Following data quality control, we analysed 22 single nucleotide polymorphisms (SNPs) on 12 candidate genes...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28510291/associations-between-rna-splicing-regulatory-variants-of-stemness-related-genes-and-racial-disparities-in-susceptibility-to-prostate-cancer
#5
Yanru Wang, Jennifer A Freedman, Hongliang Liu, Patricia G Moorman, Terry Hyslop, Daniel J George, Norman H Lee, Steven R Patierno, Qingyi Wei
Evidence suggests that cells with a stemness phenotype play a pivotal role in oncogenesis, and prostate cells exhibiting this phenotype have been identified. We used two genome-wide association study (GWAS) datasets of African descendants, from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana Prostate Study, as well as two GWAS datasets of non-Hispanic whites, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between genetic variants of stemness-related genes and racial disparities in susceptibility to prostate cancer...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28475748/associations-of-carboxypeptidase-4-with-aldh1a1-expression-and-their-prognostic-value-in-esophageal-squamous-cell-carcinoma
#6
L Sun, J Cao, C Guo, J Burnett, Z Yang, Y Ran, D Sun
Esophageal cancer is an aggressive disease with poor prognosis because of early metastasis when diagnosed and recurrence after surgery. This study is aimed at investigating the expression of carboxypeptidaseA4 (CPA4) and aldehyde dehydrogenase 1A1 (ALDH1A1) in esophageal squamous cell carcinoma (ESCC) tumor tissues and analyzed their association and clinical significance. The expression of CPA4 and ALDH1A1 was determined by immunohistochemistry using the corresponding primary antibodies on two commercial tissue arrays...
June 1, 2017: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
https://www.readbyqxmd.com/read/28449663/mir-23b-controls-aldh1a1-expression-in-cervical-cancer-stem-cells
#7
Weiwen Wang, Yang Li, Na Liu, Yu Gao, Long Li
BACKGROUND: Cancer stem cells has been widely investigated due to its essential role in cancer progression and drug resistance. Here, we try to find a new therapeutic target for cervical cancer stem cells. METHODS: We detected ALDH1A1-associated miRNAs expression in our isolated tumorspheres and their corresponding parental cells. Sphere formation assay was also used to determine stemness after cells were manipulated with miR-23b plasmid or miR-23b inhibitor. RESULTS: We found that miR-23b was under-expressed in cervical cancer stem cells to maintain high levels of ALDH1A1...
April 27, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28431580/cripto-1-acts-as-a-functional-marker-of-cancer-stem-like-cells-and-predicts-prognosis-of-the-patients-in-esophageal-squamous-cell-carcinoma
#8
Qiang Liu, Xiang Cui, Xi Yu, Bai-Shi-Jiao Bian, Feng Qian, Xu-Gang Hu, Cheng-Dong Ji, Lang Yang, Yong Ren, Wei Cui, Xia Zhang, Peng Zhang, Ji Ming Wang, You-Hong Cui, Xiu-Wu Bian
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is highly malignant with highly invasive and metastatic capabilities and poor prognosis. It is believed that the ESCC cancer stem-like cells (ECSLCs) are critical for tumorigenicity, invasion and metastasis of ESCC. However, the properties of ECSLCs vary with different markers used in isolation, so that new and more effective markers of ECSLCs need to be identified. This study aimed to estimate the potentiality of Cripto-1 (CR-1) as an ECSLC surface marker and investigate the clinical significance of CR-1 expression in ESCC...
April 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28420235/garcinol-from-garcinia-indica-downregulates-cancer-stem-like-cell-biomarker-aldh1a1-in-nonsmall-cell-lung-cancer-a549-cells-through-ddit3-activation
#9
Jinhan Wang, Liwen Wang, Chi-Tang Ho, Kunsheng Zhang, Qiang Liu, Hui Zhao
Nonsmall cell lung cancer (NSCLC) is the predominant type of lung cancer. Patients with NSCLC show high mortality rates because of failure to clean up cancer stem cells (CSCs). The anticancer activity of phytochemical garcinol has been identified in various cancer cell models. However, the effect of garcinol on NSCLC cell lines is still lacking. Of the NSCLC cell lines we tested, A549 cells were the most sensitive to garcinol. Interestingly, Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) was preferentially expressed in A549 cells and downregulated by the addition of garcinol...
April 27, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28415606/taz-induces-lung-cancer-stem-cell-properties-and-tumorigenesis-by-up-regulating-aldh1a1
#10
Jihang Yu, Adel Alharbi, Hongchao Shan, Yawei Hao, Brooke Snetsinger, Michael J Rauh, Xiaolong Yang
Recent studies suggest that lung cancer stem cells (CSCs) may play major roles in lung cancer. Therefore, identification of lung CSC drivers may provide promising targets for lung cancer. TAZ is a transcriptional co-activator and key downstream effector of the Hippo pathway, which plays critical roles in various biological processes. TAZ has been shown to be overexpressed in lung cancer and involved in tumorigenicity of lung epithelial cells. However, whether TAZ is a driver for lung CSCs and tumor formation in vivo is unknown...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389731/esophageal-cancer-stem-cells-are-suppressed-by-tranilast-a-trpv2-channel-inhibitor
#11
Atsushi Shiozaki, Michihiro Kudou, Daisuke Ichikawa, Hitoshi Fujiwara, Hiroki Shimizu, Takeshi Ishimoto, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Shuhei Komatsu, Kazuma Okamoto, Yoshinori Marunaka, Eigo Otsuji
BACKGROUND: Recent evidence suggests that the targeting of membrane proteins specifically activated in cancer stem cells (CSCs) is an important strategy for cancer therapy. The objectives of the present study were to investigate the expression and activity of ion-transport-related molecules in the CSCs of esophageal squamous cell carcinoma. METHODS: Cells exhibiting strong aldehyde dehydrogenase 1 family member A1 (ALDH1A1) activity were isolated from TE8 cells by fluorescence-activated cell sorting, and CSCs were then generated with the sphere formation assay...
April 7, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28383433/aldehyde-dehydrogenase-1-aldh1-expression-is-an-independent-prognostic-factor-in-triple-negative-breast-cancer-tnbc
#12
Fei Ma, Huihui Li, Yiqun Li, Xiaoyan Ding, Haijuan Wang, Ying Fan, Chen Lin, Haili Qian, Binghe Xu
Triple negative breast cancer (TNBC) is a subset of breast cancer that is highly aggressive and has a poor prognosis. Meanwhile, cancer stem cells (CSCs) are also characterized by a strong tumorigenic potential, which might be partly responsible for the aggressive behavior of TNBC. We previously showed that CSCs are enriched in TNBC cell lines and tissues. Further experiments in animal models revealed higher tumorigenicity of CSCs sorted from TNBC cell lines. In this study, we aimed to determine the clinical relationship between CSCs and TNBC by exploring the expression of aldehyde dehydrogenase 1 (ALDH1), which is a putative marker of breast CSCs, in TNBC tissues...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28373423/new-and-old-genes-associated-with-topotecan-resistance-development-in-ovarian-cancer-cell-lines
#13
Andrzej Klejewski, Monika Świerczewska, Katarzyna Zaorska, Maciej Brązert, Michał Nowicki, Maciej Zabel, Radosław Januchowski
BACKGROUND: Low effectiveness of chemotherapy in ovarian cancer results from development of drug resistance. Topotecan is a drug used as second-line chemotherapy for this cancer type. We analyzed development of topotecan resistance in ovarian cancer cell lines. MATERIALS AND METHODS: A chemosensitivity assay, MTT test, was performed to assess drug resistance. Quantitative polymerase chain reaction (Q-PCR) assays were performed to determine ABCB1, ABCG2, ALDH1A1, IFIH1, SAMD4 and EPHA3 gene expression...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28373070/disulfiram-suppresses-cancer-stem-like-properties-and-stat3-signaling-in-triple-negative-breast-cancer-cells
#14
Yoon-Jae Kim, Ji Young Kim, Nahyun Lee, Eunhye Oh, Daeil Sung, Tae-Min Cho, Jae Hong Seo
In the presence of copper (Cu), disulfiram (DSF) suppresses properties associated with cancer stem cells (CSCs) in breast cancer, but the mechanism of action is poorly understood. In the present study, we observed that DSF/Cu treatment induced apoptosis, mediated by caspase-3 activation in triple-negative breast cancer (TNBC) cells. DSF/Cu treatment also specifically targeted CSC-like cell populations, marked by the inhibition of ALDH1 activity, the suppression of CD44+/CD24-and CD49f+/CD24 + subpopulations, and the subsequent impairment of mammosphere formation...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28326165/neurochemical-and-motor-changes-in-mice-with-combined-mutations-linked-to-parkinson-s-disease
#15
Xiang Bai, Margaret Chia-Ying Wey, Paul Anthony Martinez, Chao Shi, Elizabeth Fernandez, Randy Strong
Considerable evidence suggests that oxidative stress plays a role in the pathogenesis of Parkinson's disease (PD), the most prevalent neurodegenerative movement disorder. Reduced expression of aldehyde dehydrogenase-1 (ALDH1) and glutathione peroxidase-1 (GPX1), enzymes that function to detoxify aldehydes and hydroxyl radicals, respectively, has been reported in the substantia nigra of patients who died with PD. To determine whether deficiency in these two genes contributes to the pathogenesis of PD, mice were generated with homozygous null mutations of both Aldh1a1 (the murine homolog of ALDH1) and Gpx1 genes [knockout (KO) mice]...
2017: Pathobiology of Aging & Age related Diseases
https://www.readbyqxmd.com/read/28280079/targeted-therapy-for-a-subset-of-acute-myeloid-leukemias-that-lack-expression-of-aldehyde-dehydrogenase-1a1
#16
Maura Gasparetto, Shanshan Pei, Mohammad Minhajuddin, Nabilah Khan, Daniel A Pollyea, Jason R Myers, John M Ashton, Michael W Becker, Vasilis Vasiliou, Keith R Humphries, Craig T Jordan, Clayton A Smith
Aldehyde dehydrogenase 1A1 (ALDH1A1) activity is high in hematopoietic stem cells and functions in part to protect stem cells from reactive aldehydes and other toxic compounds. In contrast, we found that ~25% of all acute myeloid leukemias expressed low or undetectable levels of ALDH1A1 and that this ALDH1A1- subset of leukemias correlates with good prognosis cytogenetics. ALDH1A1- cell lines as well as primary leukemia cells were found to be sensitive to treatment with compounds that directly and indirectly generate toxic ALDH substrates including 4-hydroxynonenal and the clinically relevant compounds arsenic trioxide and 4-hydroperoxycyclophosphamide...
March 9, 2017: Haematologica
https://www.readbyqxmd.com/read/28259926/suppression-of-cancer-stem-like-phenotypes-in-nci-h460-lung-cancer-cells-by-vanillin-through-an-akt-dependent-pathway
#17
Songpol Srinual, Pithi Chanvorachote, Varisa Pongrakhananon
Cancer stem cells (CSCs) have been reported as a major cause of cancer metastasis and the failure of cancer treatment. Cumulative studies have indicated that protein kinase B (Akt) and its downstream signaling pathway, including CSC markers, play a critical role in the aggressive behavior of this cancer. In this study, we investigated whether vanillin, a major component in Vanilla planifolia seed, could suppress cancer stemness phenotypes and related proteins in the human non-small cell lung cancer NCI‑H460 cell line...
February 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28219011/inhibition-of-the-aldehyde-dehydrogenase-1-2-family-by-psoralen-and-coumarin-derivatives
#18
Cameron D Buchman, Thomas D Hurley
Aldehyde dehydrogenase 2 (ALDH2), one of 19 ALDH superfamily members, catalyzes the NAD(+)-dependent oxidation of aldehydes to their respective carboxylic acids. In this study, we further characterized the inhibition of four psoralen and coumarin derivatives toward ALDH2 and compared them to the ALDH2 inhibitor daidzin for selectivity against five ALDH1/2 isoenzymes. Compound 2 (Ki = 19 nM) binds within the aldehyde-binding site of the free enzyme species of ALDH2. Thirty-three structural analogs were examined to develop a stronger SAR profile...
March 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#19
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignacio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193222/phosphorylation-dependent-regulation-of-aldh1a1-by-aurora-kinase-a-insights-on-their-synergistic-relationship-in-pancreatic-cancer
#20
Jing Wang, Kumar Nikhil, Keith Viccaro, Lei Chang, Jacoba White, Kavita Shah
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are key underlying causes that promote extensive metastasis, drug resistance, and tumor recurrence in highly lethal pancreatic cancer. The mechanisms leading to EMT and CSC phenotypes are not fully understood, which has hindered the development of effective targeted therapies capable of improving treatment outcomes in patients with pancreatic cancer. RESULTS: We show a central role of Aurora kinase A (AURKA) in promoting EMT and CSC phenotypes via ALDH1A1, which was discovered as its direct substrate using an innovative chemical genetic screen...
February 13, 2017: BMC Biology
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