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Aldh1a1

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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, Ignatio 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...
February 15, 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
#13
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
https://www.readbyqxmd.com/read/28184944/exploration-of-bladder-cancer-molecular-mechanisms-based-on-mirna-mrna-regulatory-network
#14
Wenfeng Li, Jia Liu, Di Zou, Xiaye Cai, Jingying Wang, Jinmeng Wang, Li Zhu, Liang Zhao, Rongying Ou, Yunsheng Xu
To explore the complex molecular mechanisms of bladder cancer, mRNA and miRNA expression profiles were combined for systematic analyses. A total of 18 common differentially expressed genes (DEGs) were identified from two mRNA expression datasets which consisted of 206 tumor and 74 normal tissues. Then, survival analysis based on the SurvExpress database showed that the common DEGs were able to significantly differentiate low- and high-risk groups in 4 public bladder cancer datasets (p<0.01). Notably, the tumor and normal samples were able to be almost clearly classified into 4 groups based on these identified common DEGs...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28179308/renieramycin-m-attenuates-cancer-stem-cell-like-phenotypes-in-h460-lung-cancer-cells
#15
Natchanun Sirimangkalakitti, Supakarn Chamni, Khanit Suwanborirux, Pithi Chanvorachote
BACKGROUND/AIM: Cancer stem cells (CSCs) are a subpopulation of cancer cells that possess self-renewal and differentiation capacities. CSCs contribute to drug-resistance, cancer recurrence and metastasis, thus development of CSC-targeted therapeutic strategies has recently received significant attention in cancer research. In this study, the potential efficacy of renieramycin M (RM) isolated from the sponge Xestospongia species, was examined against lung CSCs. MATERIALS AND METHODS: Colony and spheroid formation assays, as well as western blotting analysis of lung CSC protein markers were employed to determine the CSC-like phenotypes of H460 lung cancer cells after treatment with RM at non-toxic concentrations...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28148901/c-ebp%C3%AE-1-promotes-transformation-and-chemoresistance-in-ewing-sarcoma-cells
#16
Jamie D Gardiner, Lisa M Abegglen, Xiaomeng Huang, Bryce E Carter, Elizabeth A Schackmann, Marcus Stucki, Christian N Paxton, R Lor Randall, James F Amatruda, Angelica R Putnam, Heinrich Kovar, Stephen L Lessnick, Joshua D Schiffman
CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28129349/a-high-content-assay-enables-the-automated-screening-and-identification-of-small-molecules-with-specific-aldh1a1-inhibitory-activity
#17
Adam Yasgar, Steven A Titus, Yuhong Wang, Carina Danchik, Shyh-Ming Yang, Vasilis Vasiliou, Ajit Jadhav, David J Maloney, Anton Simeonov, Natalia J Martinez
Aldehyde dehydrogenase enzymes (ALDHs) have a broad spectrum of biological activities through the oxidation of both endogenous and exogenous aldehydes. Increased expression of ALDH1A1 has been identified in a wide-range of human cancer stem cells and is associated with cancer relapse and poor prognosis, raising the potential of ALDH1A1 as a therapeutic target. To facilitate quantitative high-throughput screening (qHTS) campaigns for the discovery, characterization and structure-activity-relationship (SAR) studies of small molecule ALDH1A1 inhibitors with cellular activity, we show herein the miniaturization to 1536-well format and automation of a high-content cell-based ALDEFLUOR assay...
2017: PloS One
https://www.readbyqxmd.com/read/28122729/zinc-suppresses-stem-cell-properties-of-lung-cancer-cells-through-protein-kinase-c-mediated-beta-catenin-degradation
#18
Chuanpit Ninsontia, Preeyaporn Plaimee Phiboonchaiyanan, Chayanin Kiratipaiboon, Pithi Chanvorachote
Highly tumorigenic cancer stem cells (CSCs) residing in most cancers are responsible for cancer progression and treatment failure. Zinc is an element regulator of several cell functions; however, its role in regulation of stem cell program in lung cancer has not been demonstrated. The present study reveals for the first time that zinc can suppress stem cell properties of lung cancer cells. Such findings were proved in different lung cancer cell lines (H460, H23, and H292) and it was found that CSC markers (CD133 and ALDH1A1), stem cell-associated transcription factors (Oct4, Nanog, and Sox-2), and the ability to form tumor spheroid were dramatically suppressed by zinc treatments...
January 25, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28046028/predictive-value-of-stemness-factor-sox2-in-gastric-cancer-is-associated-with-tumor-location-and-stage
#19
Lang Yang, Jun-Feng Xu, Qian Kang, Ai-Qin Li, Peng Jin, Xin Wang, Yu-Qi He, Na Li, Tao Cheng, Jian-Qiu Sheng
Cancer stem cells (CSCs) are thought to be the "root" of cancer. Although stemness-related factors ALDH1A1 and Sox2 have been used as markers to identify gastric CSCs, the expression pattern and significance of these factors in gastric cancer have not been sufficiently demonstrated. In this study, the expressions of ALDH1A1 and Sox2 were detected by immunohistochemistry in 122 gastric cancer specimens. And the correlation between Sox2 or ALDH1A1 expression and clinicopathological parameters and overall survival data were analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/27994520/evaluation-of-breast-cancer-stem-cells-and-intratumor-stemness-heterogeneity-in-triple-negative-breast-cancer-as-prognostic-factors
#20
Fang Yang, Lulu Cao, Zijia Sun, Juan Jin, Hehui Fang, Wenwen Zhang, Xiaoxiang Guan
Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness and poor prognosis of TNBC. Also, the breast cancers display frequent inter- and intra-tumor heterogeneity, which adds the complexity in diagnosis and predicting prognosis. Here we investigated the clinical relevance and prognostic value of the BCSC markers, CD44(+)/CD24(-), aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and CD133 in 88 TNBC cases...
2016: International Journal of Biological Sciences
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