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Hif-1 lung cancer

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https://www.readbyqxmd.com/read/28225008/anticancer-osmium-complex-inhibitors-of-the-hif-1%C3%AE-and-p300-protein-protein-interaction
#1
Chao Yang, Wanhe Wang, Guo-Dong Li, Hai-Jing Zhong, Zhen-Zhen Dong, Chun-Yuen Wong, Daniel W J Kwong, Dik-Lung Ma, Chung-Hang Leung
The hypoxia inducible factor (HIF) pathway has been considered to be an attractive anti-cancer target. One strategy to inhibit HIF activity is through the disruption of the HIF-1α-p300 protein-protein interaction. We report herein the identification of an osmium(II) complex as the first metal-based inhibitor of the HIF-1α-p300 interaction. We evaluated the effect of complex 1 on HIF-1α signaling pathway in vitro and in cellulo by using the dual luciferase reporter assay, co-immunoprecipitation assay, and immunoblot assay...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-receptor-expression-to-promote-metastasis
#2
Julia A Ju, Ines Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
: Metastasis is the leading cause of breast cancer (BCa)mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM binding receptors in this process was explored. Using a bioinformatics approach the expression of all integrin receptor subunits, in two independent BCa patient data sets, were analyzed to determine if integrin status correlates with a validated hypoxiainducible gene signature...
February 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#3
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28089517/hypoxia-induces-a-hif-1-dependent-transition-from-collective-to-amoeboid-dissemination-in-epithelial-cancer-cells
#4
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]...
February 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28075452/a-novel-pathway-in-nsclc-cells-mir%C3%A2-191-targeting-nfia-is-induced-by-chronic-hypoxia-and-promotes-cell-proliferation-and-migration
#5
Jia Zhao, Cheng-Rui Qiao, Zheng Ding, Yin-Liang Sheng, Xiang-Nan Li, Yang Yang, Deng-Yan Zhu, Chun-Yang Zhang, Dong-Lei Liu, Kai Wu, Song Zhao
MicroRNAs (miRs) have emerged as being important in cancer biology. miR‑191 is a conserved miRNA, which has been investigated in detail and is reported to be induced by hypoxia-inducible factor (HIF)‑1α and has an contributory action in the progression of breast, hepatic and pancreatic cancer. However, the effects of miR‑191 in the progression of lung cancer are a subject of debate. In the present study, it was found that the expression of miR-191 was significantly upregulated in non‑small cell lung cancer (NSCLC) cells in patients in vivo...
January 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28062918/glycine-decarboxylase-and-hif-1%C3%AE-expression-are-negative-prognostic-factors-in-primary-resected-early-stage-non-small-cell-lung-cancer
#6
Sabina Berezowska, José A Galván, Rupert Langer, Lukas Bubendorf, Spasenija Savic, Mathias Gugger, Ralph A Schmid, Thomas M Marti
Glycine decarboxylase (GLDC) was recently described as a critical enzyme of tumor-initiating cells and, thus, a driver of tumorigenesis in lung non-small cell cancer (NSCC). It is important in metabolism under hypoxic conditions. Hypoxia-inducible factor 1-alpha (HIF-1α) is the unique subunit that determines HIF system activity, thereby regulating the adverse effects of hypoxia on cancer outcome. We examined the expression and prognostic significance of GLDC and HIF-1α in primary resected stage I/II NSCC...
January 7, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28045433/functions-and-epigenetic-regulation-of-wwox-in-bone-metastasis-from-breast-carcinoma-comparison-with-primary-tumors
#7
REVIEW
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28042952/uncoupling-protein-2-downregulation-by-hypoxia-through-repression-of-peroxisome-proliferator-activated-receptor-%C3%AE-promotes-chemoresistance-of-non-small-cell-lung-cancer
#8
Mingxing Wang, Guoyin Li, Zhiwei Yang, Lei Wang, Lei Zhang, Ting Wang, Yimeng Zhang, Shengli Zhang, Yong Han, Lintao Jia
Hypoxic microenvironment is critically involved in the response of non-small cell lung cancer (NSCLC) to chemotherapy, the mechanisms of which remain largely unknown. Here, we found that NSCLC patients exhibited increased chemotherapeutic resistance when complicated by chronic obstructive pulmonary disease (COPD), a critical cause of chronic hypoxemia. The downregulation of uncoupling protein 2 (UCP2), which is attributed to hypoxia-inducible factor 1 (HIF-1)-mediated suppression of the transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ), was involved in NSCLC chemoresistance, and predicted a poor survival rate of patients receiving routine chemotherapy...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28031935/interaction-between-hypoxia-akt-and-hif-1-signaling-in-hnscc-and-nsclc-implications-for-future-treatment-strategies
#9
Hanneke Stegeman, Paul N Span, Wenny Jm Peeters, Marieke Mg Verheijen, Reidar Grénman, Tineke Wh Meijer, Johannes Ham Kaanders, Johan Bussink
BACKGROUND: Hypoxia is a negative prognostic factor and this study investigated the relationship between hypoxia, hypoxia inducible factor 1 (HIF-1) and AKT signaling in head and neck squamous cell carcinoma (HNSCC) and non-small-cell lung cancer (NSCLC). RESULTS/METHODOLOGY: pAKT was induced by hypoxia (0.5% O2) in a part of HNSCC (3/4) and squamous (2/3) and adenocarcinoma (1/3) NSCLS lines. AKT-inhibitor MK-2206 reduced hypoxic HIF-1 signaling in most HNSCC cell lines...
March 2016: Future Science OA
https://www.readbyqxmd.com/read/28028936/hypoxia-inducible-factor-1-promotes-chemoresistance-of-lung-cancer-by-inducing-carbonic-anhydrase-ix-expression
#10
Terumasa Sowa, Toshi Menju, Toyofumi F Chen-Yoshikawa, Koji Takahashi, Shigeto Nishikawa, Takao Nakanishi, Kei Shikuma, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Harada, Hiroshi Date
Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro...
January 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28004751/daxx-inhibits-hypoxia-induced-lung-cancer-cell-metastasis-by-suppressing-the-hif-1%C3%AE-hdac1-slug-axis
#11
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/27999195/molecular-and-functional-evaluation-of-a-novel-hif-inhibitor-benzopyranyl-1-2-3-triazole-compound
#12
Kyunghye Park, Hye Eun Lee, Sun Hee Lee, Doohyun Lee, Taeho Lee, You Mie Lee
Hypoxia occurs in a variety of pathological events, including the formation of solid tumors. Hypoxia-inducible factor (HIF)-1α is stabilized under hypoxic conditions and is a key molecule in tumor growth and angiogenesis. Seeking to develop novel cancer therapeutics, we investigated small molecules from our in-house chemical libraries to target HIF-1α. We employed a dual-luciferase assay that uses a luciferase (Luc) reporter vector harboring five copies of hypoxia-responsive element (HRE) in the promoter...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27966538/nqo1-inhibits-proteasome-mediated-degradation-of-hif-1%C3%AE
#13
Eun-Taex Oh, Jung-Whan Kim, Joon Mee Kim, Soo Jung Kim, Jae-Seon Lee, Soon-Sun Hong, Justin Goodwin, Robin J Ruthenborg, Myung Gu Jung, Hae-June Lee, Chul-Ho Lee, Eun Sung Park, Chulhee Kim, Heon Joo Park
Overexpression of NQO1 is associated with poor prognosis in human cancers including breast, colon, cervix, lung and pancreas. Yet, the molecular mechanisms underlying the pro-tumorigenic capacities of NQO1 have not been fully elucidated. Here we show a previously undescribed function for NQO1 in stabilizing HIF-1α, a master transcription factor of oxygen homeostasis that has been implicated in the survival, proliferation and malignant progression of cancers. We demonstrate that NQO1 directly binds to the oxygen-dependent domain of HIF-1α and inhibits the proteasome-mediated degradation of HIF-1α by preventing PHDs from interacting with HIF-1α...
December 14, 2016: Nature Communications
https://www.readbyqxmd.com/read/27959445/delphinidin-inhibits-angiogenesis-through-the-suppression-of-hif-1%C3%AE-and-vegf-expression-in-a549-lung-cancer-cells
#14
Mun-Hyeon Kim, Yun-Jeong Jeong, Hyun-Ji Cho, Hyang-Sook Hoe, Kwan-Kyu Park, Yoon-Yub Park, Yung Hyun Choi, Cheorl-Ho Kim, Hyeun-Wook Chang, Young-Ja Park, Il-Kyung Chung, Young-Chae Chang
Delphinidin, a polyphenol that belongs to the group of anthocyanidins and is abundant in many pigmented fruits and vegetables, possesses important antioxidant, anti‑inflammatory, anti-mutagenic and anticancer properties. In the present study, we investigated the inhibitory effects of delphinidin on vascular endothelial growth factor (VEGF) expression, an important factor involved in angiogenesis and tumor progression, in A549 human lung cancer cells. Delphinidin inhibited CoCl2- and epidermal growth factor (EGF)-induced VEGF mRNA expression and VEGF protein production...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27765573/a-polysaccharide-from-sargassum-thunbergii-inhibits-angiogenesis-via-downregulating-mmp-2-activity-and-vegf-hif-1%C3%AE-signaling
#15
Minghui Ou, Xuezhi Sun, Jiancheng Liang, Fei Liu, Liqin Wang, Xiaomin Wu, Jie Tu
A water-soluble polysaccharide (STPC2) was isolated from the boiling-water extract of Sargassum thunbergii, purified by CaCl2 precipitation and chromatography on DEAE-cellulose and Sephacryl S-300 column. It was found that STPC2, with a molecular weight of 57kD, was composed of fucose, xylose, galactose and glucuronic acid, in a ratio of 8.1: 3.8: 2.1: 1.0. Additionally, we found that STPC2 significantly inhibited endothelial cell migration and tube formation without toxicity. Moreover, STPC2 significantly inhibited lung cancer cell A549 migration and proliferation...
January 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27567539/pharmacokinetic-and-anti-cancer-properties-of-high-dose-ascorbate-in-solid-tumours-of-ascorbate-dependent-mice
#16
Elizabeth J Campbell, Margreet C M Vissers, Christina Wohlrab, Kevin O Hicks, R Matthew Strother, Stephanie M Bozonet, Bridget A Robinson, Gabi U Dachs
Despite recent evidence for an anti-tumour role for high-dose ascorbate, potential mechanisms of action are still unclear. At mM concentrations that are achieved with high-dose intravenous administration, autoxidation of ascorbate can generate cytotoxic levels of H2O2. Ascorbate is also a required co-factor for the hydroxylases that suppress the transcription factor hypoxia-inducible factor (HIF-1). HIF-1 supports an aggressive tumour phenotype and is associated with poor prognosis, and previous studies have shown that optimizing intracellular ascorbate levels down-regulates HIF-1 activation...
August 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27566589/ermp1-a-novel-potential-oncogene-involved-in-upr-and-oxidative-stress-defense-is-highly-expressed-in-human-cancer
#17
Alberto Grandi, Alice Santi, Susanna Campagnoli, Matteo Parri, Elisa De Camilli, Chaojun Song, Boquan Jin, Aurelien Lacombe, Serenella Castori-Eppenberger, Paolo Sarmientos, Guido Grandi, Giuseppe Viale, Luigi Terracciano, Paola Chiarugi, Piero Pileri, Renata Grifantini
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are highly activated in cancer and involved in tumorigenesis and resistance to anti-cancer therapy. UPR is becoming a promising target of anti-cancer therapies. Thus, the identification of UPR components that are highly expressed in cancer could offer new therapeutic opportunity.In this study, we demonstrate that Endoplasmic Reticulum Metallo Protease 1 (ERMP1) is broadly expressed in a high percentage of breast, colo-rectal, lung, and ovary cancers, regardless of their stage and grade...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27562754/anti-inflammatory-effects-of-phyllanthus-emblica-l-on-benzopyrene-induced-precancerous-lung-lesion-by-regulating-the-il-1%C3%AE-mir-101-lin28b-signaling-pathway
#18
Cheng-Cheng Wang, Jia-Rui Yuan, Chun-Fei Wang, Nan Yang, Juan Chen, Dan Liu, Jie Song, Liang Feng, Xiao-Bin Tan, Xiao-Bin Jia
BACKGROUND: Phyllanthus emblica L (PEL), a well-known medical plant, has been used in Asian countries for a long time. Increasing evidence suggests that it can prevent the tumorigenesis of cancer associated with nonresolving inflammation. However, the possible anti-inflammatory mechanism responsible for preventing tumorigenesis of precancerous lung lesions is not well elucidated. MATERIALS AND METHODS: Male A/J mice were randomly divided into 5 groups with 10 mice in each group: (1) blank group (saline), (2) benzo(a)pyrene [B(a)P] group, (3) and (4) B(a)P + PEL (5 g/kg/d, 10 g/kg/d, administered by gavage), (5) B(a)P + celecoxib (30 mg/kg/d, administered by gavage)...
August 24, 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/27553958/inhibition-of-notch-and-hif-enhances-the-antitumor-effect-of-radiation-in-notch-expressing-lung-cancer
#19
Yasuyuki Ikezawa, Jun Sakakibara-Konishi, Hidenori Mizugaki, Satoshi Oizumi, Masaharu Nishimura
BACKGROUND: The Notch receptor plays an important role in various cell fate decisions during development and in cancer. We have previously reported that Notch3 is upregulated by radiation in non-small cell lung cancer (NSCLC) cell lines and that the Notch pathway inhibitor γ secretase inhibitor GSI (gamma-secretase inhibitor), when combined with radiation therapy, significantly suppressed the growth of lung cancer cells. However, little is known about the mechanism of Notch upregulation induced by radiation...
February 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27499160/hypoxia-upregulates-malat1-expression-through-a-camkk-ampk-hif-1%C3%AE-axis
#20
Sandrine Sallé-Lefort, Stéphanie Miard, Marc-André Nolin, Louise Boivin, Marie-Ève Paré, Richard Debigaré, Frédéric Picard
Increased expression levels of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) have been associated with enhanced proliferation and metastasis of several cancer cell types. Hypoxia, a hallmark characteristic of solid tumors, has been linked to an increase in the activity of the ATP-generating AMPK protein. Since Malat1 was recently shown to be upregulated during hypoxia, the objective of this study was to determine the contribution of AMPK in the mechanistic pathways regulating Malat1 expression in low oxygen conditions...
October 2016: International Journal of Oncology
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