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https://www.readbyqxmd.com/read/28089517/hypoxia-induces-a-hif-1-dependent-transition-from-collective-to-amoeboid-dissemination-in-epithelial-cancer-cells
#1
Steffi Lehmann, Veronika Te Boekhorst, Julia Odenthal, Roberta Bianchi, Sjoerd van Helvert, Kristian Ikenberg, Olga Ilina, Szymon Stoma, Jael Xandry, Liying Jiang, Reidar Grenman, Markus Rudin, Peter Friedl
Cancer metastases arise from a multi-step process that requires metastasizing tumor cells to adapt to signaling input from varying tissue environments [1]. As an early metastatic event, cancer cell dissemination occurs through different migration programs, including multicellular, collective, and single-cell mesenchymal or amoeboid migration [2-4]. Migration modes can interconvert based on changes in cell adhesion, cytoskeletal mechanotransduction [5], and/or proteolysis [6], most likely under the control of transcriptional programs such as the epithelial-to-mesenchymal transition (EMT) [7, 8]...
January 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28088787/hint2-downregulation-promotes-colorectal-carcinoma-migration-and-metastasis
#2
Weihua Li, Shaoxin Cai, Le Wang, Changshun Yang, Biaohuan Zhou, Huan Wang
Histidine triad nucleotide-binding 2 (HINT2), a member of the histidine triad proteins family, sensitizes cells to apoptosis in hepatocellular carcinoma. Here, we showed that HINT2 expression is lower in primary colorectal cancer (CRC) and metastasis tissues than in normal colorectal tissues, and that HINT2 abundance is inversely correlated with CRC tumor stage. Treating CRC cells with 5-aza-2'-deoxycytidine, a demethylating agent, upregulated HINT2, suggesting HINT2 downregulation is caused by methylation of the gene promoter...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28079892/hif-2%C3%AE-and-oct4-have-synergistic-effects-on-survival-and-myocardial-repair-of-very-small-embryonic-like-mesenchymal-stem-cells-in-infarcted-hearts
#3
Shaoheng Zhang, Lan Zhao, Jiahong Wang, Nannan Chen, Jian Yan, Xin Pan
Poor cell survival and limited functional benefits have restricted mesenchymal stem cell (MSC) efficacy for treating myocardial infarction (MI), suggesting that a better understanding of stem cell biology is needed. The transcription factor HIF-2α is an essential regulator of the transcriptional response to hypoxia, which can interact with embryonic stem cells (ESCs) transcription factor Oct4 and modulate its signaling. Here, we obtained very small embryonic-like mesenchymal stem cells (vselMSCs) from MI patients, which possessed the very small embryonic-like stem cells' (VSELs) morphology as well as ESCs' pluripotency...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28077595/long-non-coding-rna-linc00152-promotes-gallbladder-cancer-metastasis-and-epithelial-mesenchymal-transition-by-regulating-hif-1%C3%AE-via-mir-138
#4
Qiang Cai, Zhenqiang Wang, Shouhua Wang, Mingzhe Weng, Di Zhou, Chen Li, Jiandong Wang, Erzhen Chen, Zhiwei Quan
Long non-coding RNA LINC00152 had been reported as an oncogene in gastric and hepatocellular cancer. In this study, we show that LINC00152 is overexpressed in gallbladder cancer (GBC) tissue samples and cell lines. The high LINC00152 levels correlated negatively with the overall survival time in GBC patients. Functionally, LINC00152 dramatically promoted cell migration, invasion and epithelial-mesenchymal transition (EMT) progression in vitro. In vivo, LINC00152 overexpression significantly promoted tumour peritoneal spreading and metastasis...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28076840/hif-1%C3%AE-induces-the-epithelial-mesenchymal-transition-in-gastric-cancer-stem-cells-through-the-snail-pathway
#5
Shi-Wei Yang, Zhi-Gang Zhang, Ying-Xue Hao, Yong-Liang Zhao, Feng Qian, Yan Shi, Ping-Ang Li, Chun-Yang Liu, Pei-Wu Yu
Substantial evidence suggests that the epithelial-mesenchymal transition (EMT) phenotype is associated with the invasive characteristics of cancer stem cells (CSCs),which possess an EMT phenotype that may predominate in tumor invasion and metastasis. However, the mechanisms for the generation and regulation of these CSCs have not been clearly defined. As hypoxia and EMT-related factors may have important functions in EMT-like CSCs, the aim of this study was to investigate the effects of hypoxia on these cells...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28070036/-hypoxic-condition-promotes-olfactory-mucosa-mesenchymal-stem-cells-to-differentiate-into-neurons-and-%C3%A2-underlying-mechanisms
#6
Yi Zhuo, Ting Yuan, Da Duan, Lei Wang, Lite Ge, Pei Wu, Hao Wang, Ming Lu
To explore whether hypoxic condition could promote the olfactory mucosa mesenchymal stem cells (OM-MSCs) to differentiate into neurons with the olfactory ensheathing cells (OECs) supernatant and the potential mechanisms.
 Methods: The OM-MSCs and OECs were isolated and cultured, and they were identified by flow cytometry and immunofluorescence. The OM-MSCs were divided into three groups: a 3%O2+ HIF-1α inhibitors (lificiguat: YC-1) + OECs supernatant group (Group A) , a 3%O2 + OECs supernatant group (Group B) and a 21%O2 + OECs supernatant group (Control group)...
December 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28069592/mir-142-modulates-human-pancreatic-cancer-proliferation-and-invasion-by-targeting-hypoxia-inducible-factor-1-hif-1%C3%AE-in-the-tumor-microenvironments
#7
Yebin Lu, Niandong Ji, Wei Wei, Weijia Sun, Xuejun Gong, Xitao Wang
MicroRNAs regulate most protein-coding genes, including genes important in cancer and other diseases. In our study, we demonstrated that the expression of miR-142 could be significantly suppressed in pancreatic cancer specimens and cell lines, comparing to their adjacent tissues and normal pancreatic cells. Growth and invasion of PANC-1 and SW1990 cells were attenuated by overexpression of miR-142 in vitro With the help of bioinformatics analysis, hypoxia-inducible factor 1 (HIF-1α) was identified to be a direct target of miR-142, and luciferase reporter experiment confirmed this discovery...
January 9, 2017: Biology Open
https://www.readbyqxmd.com/read/28012234/hypoxia-promotes-the-phenotypic-change-of-aldehyde-dehydrogenase-activity-of-breast-cancer-stem-cells
#8
Akira Shiraishi, Kana Tachi, Nesrine Essid, Ikki Tsuboi, Masumi Nagano, Toshiki Kato, Toshiharu Yamashita, Hiroko Bando, Hisato Hara, Osamu Ohneda
Stable breast cancer cell (BCC) lines are valuable tools for the identification of breast cancer stem cell (BCSC) phenotypes that develop in response to several stimuli as well as for studying the basic mechanisms associated with the initiation and maintenance of BCSCs. However, the characteristics of individual, BCC-derived BCSCs varies and these cells show distinct phenotypes depending on the different BCSC markers used for their isolation. Aldehyde dehydrogenase (ALDH) activity is just such a recognized biomarker of BCSCs with a CD44(+) /CD24(-) phenotype...
December 23, 2016: Cancer Science
https://www.readbyqxmd.com/read/28004751/daxx-inhibits-hypoxia-induced-lung-cancer-cell-metastasis-by-suppressing-the-hif-1%C3%AE-hdac1-slug-axis
#9
Ching-Wen Lin, Lu-Kai Wang, Shu-Ping Wang, Yi-Liang Chang, Yi-Ying Wu, Hsuan-Yu Chen, Tzu-Hung Hsiao, Wei-Yun Lai, Hsuan-Hsuan Lu, Ya-Hsuan Chang, Shuenn-Chen Yang, Ming-Wei Lin, Chi-Yuan Chen, Tse-Ming Hong, Pan-Chyr Yang
Hypoxia is a major driving force of cancer invasion and metastasis. Here we show that death domain-associated protein (Daxx) acts to negatively regulate hypoxia-induced cell dissemination and invasion by inhibiting the HIF-1α/HDAC1/Slug pathway. Daxx directly binds to the DNA-binding domain of Slug, impeding histone deacetylase 1 (HDAC1) recruitment and antagonizing Slug E-box binding. This, in turn, stimulates E-cadherin and occludin expression and suppresses Slug-mediated epithelial-mesenchymal transition (EMT) and cell invasiveness...
December 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/28000883/2-methoxyestradiol-inhibits-the-proliferation-and-migration-and-reduces-the-radioresistance-of-nasopharyngeal-carcinoma-cne-2-stem-cells-via-nf-%C3%AE%C2%BAb-hif-1-signaling-pathway-inactivation-and-emt-reversal
#10
Shun-Long Wu, Ya-Jun Li, Kui Liao, Lei Shi, Na Zhang, Shuang Liu, Yao-Yao Hu, Shao-Lin Li, Ying Wang
Accumulating evidence indicates that cancer stem cells (CSCs) are a source of resistance to radiation therapy (RT); however, the mechanism of this resistance remains unclear. 2-Methoxyestradiol (2-ME2) is a metabolic product of estrogen in the body. Recent studies have found that 2-ME2 regulates the activation of transcription factors, including nuclear factor (NF)-κB/hypoxia-inducible factor-1 (HIF-1), thus contributing to tumor cell apoptosis and chemosensitivity. Therefore, 2-ME2 is being studied as a potential anticancer drug...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27987431/acriflavine-inhibits-acquired-drug-resistance-by-blocking-the-epithelial-to-mesenchymal-transition-and-the-unfolded-protein-response
#11
Jeroen Dekervel, Ashenafi Bulle, Petra Windmolders, Diether Lambrechts, Eric Van Cutsem, Chris Verslype, Jos van Pelt
: Epithelial-to-mesenchymal transition (EMT) is linked to tumor invasion, drug resistance and aggressive disease and this is largely dependent on the cell's microenvironment. Acriflavine (ACF) is an old antibacterial drug recently also suggested as anticancer agent and HIF inhibitor. We wanted to study the effect of acriflavine on EMT in different human cancer models. Pancreatic cancer cells (Panc-1) were exposed to TGF-β1 or cobalt chloride (to mimick severe hypoxia) to induce EMT. For our third model we exposed HepG2 liver cancer cells to sorafenib which resulted in development of acquired drug resistance with strong features of EMT and aggressive behavior...
December 14, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27983915/kallistatin-suppresses-cell-proliferation-invasion-and-promotes-apoptosis-in-cervical-cancer-through-blocking-nf-%C3%AE%C2%BAb-signaling
#12
Tao Wang, Fan Shi, JiQuan Wang, Zi Liu, Jin Su
Kallistatin has been recognized as an endogenous angiogenesis inhibitor, and exerts pleiotropic effects in inhibiting tumor growth, migration, apoptosis and inflammation. The purpose of the present study was to investigate the potential role and mechanisms of kallistatin in cervical cancer. We demonstrated that kallistatin effectively inhibited cell proliferation and enhanced apoptosis in a dose-dependent manner. Additionally, kallistatin suppressed migration and invasion activity as well as markedly reduced the expression of matrix-degrading metalloproteinases, progelatinase (MMP-2), MMP-9 and urokinase-type PA (uPA)...
November 24, 2016: Oncology Research
https://www.readbyqxmd.com/read/27981247/aspartate-%C3%AE-hydroxylase-asph-a-potential-therapeutic-target-in-human-malignant-gliomas
#13
Lisa-Marie Sturla, Ming Tong, Nick Hebda, Jinsong Gao, John-Michael Thomas, Mark Olsen, Suzanne M de la Monte
BACKGROUND: Despite therapeutic advances, survival with glioblastoma multiforme (GBM) remains below 15 months from diagnosis due to GBM's highly infiltrative nature which precludes complete surgical resection. Patient outcomes could potentially be improved by targeting genes and pathways that drive neoplastic cell motility and invasiveness, including hypoxia-inducible factor-1 (HIF-1α), NOTCH, and aspartate-β-hydroxylase (ASPH). METHODS: Human astrocytoma biopsy specimens (n = 37), WHO Grades II-IV, were analyzed for levels and distributions of ASPH and HIF-1α immunoreactivity by immunohistochemical staining, and ASPH, Notch, JAG, HES1, HEY1 and HIF1α mRNA expression by quantigene multiplex analysis...
December 2016: Heliyon
https://www.readbyqxmd.com/read/27966740/hypoxia-facilitates-epithelial-mesenchymal-transition-mediated-rectal-cancer-progress
#14
L L Sun, Z Song, W Z Li, S Y Tang
Rectal cancer is a commonly observed tumor in clinics, and epithelial-mesenchymal transition (EMT) is very important for tumor invasion and metastasis. We established a rectal cancer HCT-116 cell hypoxia model and detected cell proliferation, invasion, and EMT-related protein expression in this model, aiming to analyze the effect of hypoxia on rectal cancer cell EMT. Rectal cancer cell line HCT-116 was cultured in normoxic, hypoxic, or anaerobic environment, and hypoxia-inducible factor-1α (HIF-1α) mRNA expression was detected in the cells by real-time PCR...
December 2, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27940158/inactivation-of-maternal-hif-1%C3%AE-at-mid-pregnancy-causes-placental-defects-and-deficits-in-oxygen-delivery-to-the-fetal-organs-under-hypoxic-stress
#15
Doreswamy Kenchegowda, Bryony Natale, Maria A Lemus, David R Natale, Steven A Fisher
A critical transition occurs near mid-gestation of mammalian pregnancy. Prior to this transition, low concentrations of oxygen (hypoxia) signaling through Hypoxia Inducible Factor (HIF) functions as a morphogen for the placenta and fetal organs. Subsequently, functional coupling of the placenta and fetal cardiovascular system for oxygen (O2) transport is required to support the continued growth and development of the fetus. Here we tested the hypothesis that Hif-1α is required in maternal cells for placental morphogenesis and function...
December 9, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27938938/overexpression-of-hif-1%C3%AE-in-mesenchymal-stem-cells-contributes-to-repairing-hypoxic-ischemic-brain-damage-in-rats
#16
Deju Lin, Liping Zhou, Biao Wang, Lizhen Liu, Li Cong, Chuanqin Hu, Tingting Ge, Qin Yu
Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage...
December 6, 2016: Comptes Rendus Biologies
https://www.readbyqxmd.com/read/27934968/k63-polyubiquitinated-hausp-deubiquitinates-hif-1%C3%AE-and-dictates-h3k56-acetylation-promoting-hypoxia-induced-tumour-progression
#17
Han-Tsang Wu, Yi-Chih Kuo, Jung-Jyh Hung, Chi-Hung Huang, Wei-Yi Chen, Teh-Ying Chou, Yeh Chen, Yi-Ju Chen, Yu-Ju Chen, Wei-Chung Cheng, Shu-Chun Teng, Kou-Juey Wu
Intratumoural hypoxia induces HIF-1α and promotes tumour progression, metastasis and treatment resistance. HIF-1α stability is regulated by VHL-E3 ligase-mediated ubiquitin-dependent degradation; however, the hypoxia-regulated deubiquitinase that stabilizes HIF-1α has not been identified. Here we report that HAUSP (USP7) deubiquitinase deubiquitinates HIF-1α to increase its stability, induce epithelial-mesenchymal transition and promote metastasis. Hypoxia induces K63-linked polyubiquitinated HAUSP at lysine 443 to enhance its functions...
December 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27926487/egf-induces-epithelial-mesenchymal-transition-and-cancer-stem-like-cell-properties-in-human-oral-cancer-cells-via-promoting-warburg-effect
#18
Qilin Xu, Qunzhou Zhang, Yasutaka Ishida, Souren Hajjar, Xudong Tang, Haoran Shi, Chi V Dang, Anh D Le
"Warburg effect", the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27915020/multifunctions-of-dual-zn-mg-ion-co-implanted-titanium-on-osteogenesis-angiogenesis-and-bacteria-inhibition-for-dental-implants
#19
Yiqiang Yu, Guodong Jin, Yang Xue, Donghui Wang, Xuanyong Liu, Jiao Sun
: In order to improve the osseointegration and long-term survival of dental implants, it is urgent to develop a multifunctional titanium surface which would simultaneously have osteogeneic, angiogeneic and antibacterial properties. In this study, a potential dental implant material-dual Zn/Mg ion co-implanted titanium (Zn/Mg-PIII) was developed via plasma immersion ion implantation (PIII). The Zn/Mg-PIII surfaces were found to promote initial adhesion and spreading of rat bone marrow mesenchymal stem cells (rBMSCs) via the upregulation of the gene expression of integrin α1 and integrin β1...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27903985/the-tissue-inhibitor-of-metalloproteinases-1-timp-1-promotes-survival-and-migration-of-acute-myeloid-leukemia-cells-through-cd63-pi3k-akt-p21-signaling
#20
Dorian Forte, Valentina Salvestrini, Giulia Corradi, Lara Rossi, Lucia Catani, Roberto M Lemoli, Michele Cavo, Antonio Curti
We and others have shown that the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), a member of the inflammatory network exerting pleiotropic effects in the bone marrow (BM) microenvironment, regulates the survival and proliferation of different cell types, including normal hematopoietic progenitor cells. Moreover, TIMP-1 has been shown to be involved in cancer progression. However, its role in leukemic microenvironment has not been addressed. Here, we investigated the activity of TIMP-1 on Acute Myelogenous Leukemia (AML) cell functions...
November 26, 2016: Oncotarget
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