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Hypoxia and metastasis

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https://www.readbyqxmd.com/read/28632992/targeting-the-rhogtpase-rock-pathway-for-the-treatment-of-vhl-hif-pathway-driven-cancers
#1
Jordan M Thompson, Jaime Landman, Olga V Razorenova
The loss of the von Hippel-Lindau (VHL) tumor-suppressor is a major driver of Clear Cell Renal Cell Carcinoma (CC-RCC) resulting in the stabilization and overactivation of hypoxia inducible factors (HIFs). ROCK 1 is a well-known protein serine/threonine kinase which is recognized as having a role in cancer including alterations in cell motility, metastasis and angiogenesis. As a function of the later effect, we recently investigated and identified a synthetic lethal interaction between VHL loss and ROCK1 inhibition in CC-RCC that is dependent on HIF overactivation...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28631600/inhibition-of-carbonic-anhydrase-ix-by-ureidosulfonamide-inhibitor-u104-reduces-prostate-cancer-cell-growth-but-does-not-modulate-daunorubicin-or-cisplatin-cytotoxicity
#2
Anne Riemann, Antje Güttler, Verena Haupt, Henri Wichmann, Sarah Reime, Matthias Bache, Dirk Vordermark, Oliver Thews
Carbonic anhydrase IX has emerged as a promising target for cancer therapy. It is highly up-regulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells in concern of potential therapeutic implications...
June 19, 2017: Oncology Research
https://www.readbyqxmd.com/read/28630300/g9a-drives-hypoxia-mediated-gene-repression-for-breast-cancer-cell-survival-and-tumorigenesis
#3
Francesco Casciello, Fares Al-Ejeh, Greg Kelly, Donal J Brennan, Shin Foong Ngiow, Arabella Young, Thomas Stoll, Karolina Windloch, Michelle M Hill, Mark J Smyth, Frank Gannon, Jason S Lee
G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse factor in tumor growth and metastasis, the role of G9a in regulating gene expression in hypoxia has not been described extensively. Here, we show that G9a protein stability is increased in hypoxia via reduced proline hydroxylation and, hence, inefficient degradation by the proteasome...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28627686/hypoxia-and-acidosis-driven-aberrations-of-secreted-micrornas-in-endometrial-cancer-in-vitro
#4
Julia Eismann, Marc Hirschfeld, Thalia Erbes, Gerta Rücker, Markus Jäger, Andrea Ritter, Daniela Weiss, Gerald Gitsch, Sebastian Mayer
Due to their post-transcriptional regulatory impact on gene expression, microRNAs (miRNA, miRs) influence decisively cellular processes of differentiation, proliferation and apoptosis. In oncogenic pathways various miRNAs exert either oncogenic or tumor suppressor activities in a stage-specific manner. Dysregulation of miRNA expression pattern has been associated with several human cancers including endometrial cancer (EC). In the present study, expression profile alterations of EC associated secreted miRNAs were determined under the microenvironmental stress situations hypoxia and acidosis occurring in tumor progression and metastasis...
June 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28624797/lymph-node-metastasis-and-the-physicochemical-micro-environment-of-pancreatic-ductal-adenocarcinoma-xenografts
#5
Lise Mari K Andersen, Catherine S Wegner, Trude G Simonsen, Ruixia Huang, Jon-Vidar Gaustad, Anette Hauge, Kanthi Galappathi, Einar K Rofstad
Pancreatic ductal adenocarcinoma (PDAC) patients develop lymph node metastases early and have a particularly poor prognosis. The poor prognosis has been shown to be associated with the physicochemical microenvironment of the tumor tissue, which is characterized by desmoplasia, abnormal microvasculature, extensive hypoxia, and highly elevated interstitial fluid pressure (IFP). In this study, we searched for associations between lymph node metastasis and features of the physicochemical microenvironment in an attempt to identify mechanisms leading to metastatic dissemination and growth...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624448/identification-of-functional-hypoxia-inducible-factor-response-elements-in-the-human-lysyl-oxidase-gene-promoter
#6
Victoria Wang, David A Davis, Robert Yarchoan
Human lysyl oxidase (LOX) is a hypoxia-responsive gene whose product catalyzes collagen crosslinking and is thought to be important in cancer metastasis and osteoarthritis. We previously demonstrated that LOX was upregulated by hypoxia inducible factor 2 (HIF-2) more strongly than hypoxia inducible 1 (HIF-1). We further investigated the response of the LOX gene and LOX promoter to HIFs. LOX mRNA, measured by real time reverse transcriptase-PCR, was strongly up-regulated (almost 40-fold), by transfection of HEK-293T cells with a plasmid encoding the HIF-2α subunit of HIF-2, but only three-fold by a plasmid encoding HIF-1α...
June 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28623514/the-potential-roles-of-bacteria-to-improve-radiation-treatment-outcome
#7
REVIEW
E Kouhsari, A Ghadimi-Daresajini, H Abdollahi, N Amirmozafari, S R Mahdavi, S Abbasian, S H Mousavi, H F Yaseri, M Moghaderi
Many combined therapies have been proposed to enhance radiotherapy outcome, but they have several limitations. As a new feasible strategy, combination of radiotherapy with bacteria showed a significant positive impact on the tumor treatment and metastasis inhibition. Although probiotic bacteria and radiotherapy alone can be effective in the treatment of different cancers, the combination of these two therapies seems to enhance therapeutic outcome and is cost-effective. Bacterial cells can act as therapeutic/gene/drug delivery vehicles as well as theranostic agents...
June 16, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28618937/37lrp-induces-invasion-in-hypoxic-lung-adenocarcinoma-cancer-cells-a549-through-the-jnk-erk-c-jun-signaling-cascade
#8
Yongan Zhou, Yafang Wang, Zhengwei Zhao, Yanxia Wang, Ning Zhang, Helong Zhang, Lili Liu
We previously reported that 37-kDa laminin receptor precursor involved in metastasis of lung adenocarcinoma cancer cells. In this study, we further revealed that hypoxia induced 37-kDa laminin receptor precursor expression and activation of extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase in lung adenocarcinoma cancer cells. In addition, we further demonstrated that the c-Jun N-terminal kinase inhibitor SP600125 and extracellular signal-regulated protein kinase inhibitor U0126 blocked the c-Jun activity and abolished hypoxia-induced 37-kDa laminin receptor precursor expression and promoter activity in a concentration-dependent manner...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617447/targeting-the-vasculature-in-hepatocellular-carcinoma-treatment-starving-versus-normalizing-blood-supply
#9
Ken Liu, Xiang Zhang, Weiqi Xu, Jinbiao Chen, Jun Yu, Jennifer R Gamble, Geoffrey W McCaughan
Traditional treatments for intermediate or advanced stage hepatocellular carcinoma (HCC) such as transarterial chemoembolization (TACE) and anti-angiogenesis therapies were developed to starve tumor blood supply. A new approach of normalizing structurally and functionally abnormal tumor vasculature is emerging. While TACE improves survival in selected patients, the resulting tumor hypoxia stimulates proliferation, angiogenesis, treatment resistance and metastasis, which limits its overall efficacy. Vessel normalization decreases hypoxia and improves anti-tumor immune infiltrate and drug delivery...
June 15, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28616914/-expressions-and-significance-of-aldh1-hif-1%C3%AE-and-vegf-in-laryngeal-squamous-cell-carcinoma
#10
Yan Zhao, Xin Jin, Nan Li, Yan-Zi Qin, Jun Qian
OBJECTIVES: To investigate the expressions of aldehyde dehydrogenase 1(ALDH1), hypoxia-inducible factor 1α(HIF-1α), vascular endothelial growth factor (VEGF) in laryngeal squamous cell carcinoma(LSCC) and their relationships with clinical significance. METHODS: In situ hybridization (ISH) method and immuohistochemical staining were used to detect the mRNA and protein expressions of ALDH1, HIF-1α and VEGF in 120 LSCC specimens and 60 cases of normal laryngeal tissue...
May 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28610954/feedback-regulation-of-aldoa-activates-the-hif-1%C3%AE-mmp9-axis-to-promote-lung-cancer-progression
#11
Yu-Chan Chang, Yung-Chieh Chan, Wei-Ming Chang, Yuan-Feng Lin, Chih-Jen Yang, Chia-Yu Su, Ming-Shyan Huang, Alexander T H Wu, Michael Hsiao
Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC)...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28608600/the-hypoxia-il1a-axis-promotes-gastric-cancer-progression-and-drug-resistance
#12
Yi Xuan, Yanong Wang
AIM: Tumor microenvironment constitutes a unique niche that promotes cancer metastasis and resistance. Two remarkable characteristics of this microenvironment are hypoxia and inflammation. Interleukin-1 alpha (IL1A), an important inflammatory factor, is frequently upregulated in a variety of cancers. Herein, we set force to characterize IL1A expression in gastric cancer and explore the relationship between IL1A and hypoxia. METHODS: Reverse-transcriptase PCR (RT-PCR) was performed to characterize IL1A expression in different gastric cancer cell lines under normonia or hypoxia...
June 13, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28606154/microrna-1296-inhibits-metastasis-and-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-by-targeting-srpk1-mediated-pi3k-akt-pathway
#13
Qiuran Xu, Xin Liu, Zhikui Liu, Zhenyu Zhou, Yufeng Wang, Jianfeng Tu, Lijie Li, Hangxing Bao, Liu Yang, Kangsheng Tu
BACKGROUND: Increasing evidences demonstrate that miRNAs contribute to development and progression of hepatocellular carcinoma (HCC). Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. However, the expression and role of miR-1296 in HCC remain unknown. METHODS: The levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. Immunoblotting and immunofluorescence were used for detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells...
June 12, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28602978/tanshinone-iiainhibits-%C3%AE-catenin-vegf-mediated-angiogenesis-by-targeting-tgf-%C3%AE-1-in-normoxic-and-hif-1%C3%AE-inhypoxicmicroenvironments-in-human-colorectal-cancer
#14
Hua Sui, Jihui Zhao, Lihong Zhou, Haotian Wen, Wanli Deng, Chunpu Li, Qing Ji, Xuan Liu, Yuanyuan Feng, Ni Chai, Qibo Zhang, Jianfeng Cai, Qi Li
In a previous study, we demonstrated that Tanshinone IIA effectively inhibits CRC angiogenesis in vivo, but the underlying mechanisms were not elucidated. In this report, we describe experiments in which HIF-1α levels were manipulated to probe the effect of hypoxia on CRC cell angiogenesis. We studied the effects of Tan IIA on CRC pro-angiogenic factor and on human umbilical vein endothelial cell angiogenesis in normoxia and hypoxia. Our results show that Tan IIA not only lowers HIF-1α levels and inhibits secretion of VEGF and bFGF, but also efficiently suppresses the proliferation, tube formation and metastasis of HUVECs...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28599281/hif-2%C3%AE-promotes-the-formation-of-vasculogenic-mimicry-in-pancreatic-cancer-by-regulating-the-binding-of-twist1-to-the-ve-cadherin-promoter
#15
Jian Yang, Dong-Ming Zhu, Xiao-Gang Zhou, Ni Yin, Yi Zhang, Zi-Xiang Zhang, De-Chun Li, Jian Zhou
Vasculogenic mimicry (VM) is a blood supply modality that occurs independently of endothelial cell angiogenesis. Hypoxia and the epithelial-mesenchymal transition (EMT) induce VM formation by remodeling the extracellular matrix. Our previous study demonstrated that hypoxia-inducible factor-2 alpha (HIF-2α) promotes the progress of EMT in pancreatic cancer; however, whether HIF-2α promotes VM formation in pancreatic cancer remains unknown. In this study, we investigated HIF-2α expression and VM by immunohistochemistry in 70 pancreatic cancer patients as well as the role of Twist1and Twist2 in HIF-2α-induced VM in vitro and in vivo...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28597139/hypoxia-and-bone-metastatic-disease
#16
REVIEW
Rachelle W Johnson, Miranda E Sowder, Amato J Giaccia
PURPOSE OF REVIEW: This review highlights our current knowledge of oxygen tensions in the bone marrow, and how low oxygen tensions (hypoxia) regulate tumor metastasis to and colonization of the bone marrow. RECENT FINDINGS: The bone marrow is a relatively hypoxic microenvironment, but oxygen tensions fluctuate throughout the marrow cavity and across the endosteal and periosteal surfaces. Recent advances in imaging have made it possible to better characterize these fluctuations in bone oxygenation, but technical challenges remain...
June 8, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28589145/metastasis-associated-protein-1-is-involved-in-angiogenesis-after-transarterial-chemoembolization-treatment
#17
Tao Xue, Wenming Feng, Hongbin Yu, Ming Zhu, Maoyun Fei, Ying Bao, Xiaoyi Wang, Wenxue Ma, Guiyuan Lv, Jianming Guan, Suhong Chen
BACKGROUND: Transarterial chemoembolization (TACE), a well-established treatment for unresectable hepatocellular carcinoma (HCC), blocks the arterial blood supply to the tumor, which can be short-lived as development of collateral neovessels, leading to the failure of treatment. Metastasis-associated protein 1 (MTA1) is involved in development of tumors and metastases. However, the role of MTA1 in angiogenesis is still obscure. METHODS: We detected the expression of MTA1 and hypoxia-inducible factor-1α (HIF-1α) and microvessel density (MVD) value in liver tumor tissues and tumor periphery before and after TACE treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28574600/diallyl-trisulfides-a-natural-histone-deacetylase-inhibitor-attenuate-hif-1%C3%AE-synthesis-and-decreases-breast-cancer-metastasis
#18
Zhonghong Wei, Yunlong Shan, Li Tao, Yuping Liu, Zhijie Zhu, Zhaoguo Liu, Yuanyuan Wu, Wenxing Chen, Aiyun Wang, Yin Lu
Intratumoral hypoxia promotes the distant metastasis of cancer subclones. The clinical expression level of hypoxia-inducible factor-1α (HIF-1α) reflects the prognosis of a variety of cancers, especially breast cancer. Histone deacetylase (HDAC) inhibitors can target HIF-1α protein due to von Hippel-Lindau protein-dependent degradation. Dietary organosulfur compounds, such as those in garlic, have been reported as HDAC inhibitors. The effects of diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) on the ratio of firefly/Renilla luciferase activity in hypoxic MDA-MB-231 cells were determined...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28562340/cell-type-dependent-hif1-%C3%AE-mediated-effects-of-hypoxia-on-proliferation-migration-and-metastatic-potential-of-human-tumor-cells
#19
Enikő Tátrai, Alexandra Bartal, Alexandra Gacs, Sándor Paku, István Kenessey, Tamás Garay, Balázs Hegedűs, Eszter Molnár, Mihály T Cserepes, Zita Hegedűs, Nóra Kucsma, Gergely Szakács, József Tóvári
Tumor hypoxia promotes neoangiogenesis and contributes to the radio- and chemotherapy resistant and aggressive phenotype of cancer cells. However, the migratory response of tumor cells and the role of small GTPases regulating the organization of cytoskeleton under hypoxic conditions have yet to be established. Accordingly, we measured the proliferation, migration, RhoA activation, the mRNA and protein levels of hypoxia inducible factor-1alpha (HIF-1α) and three small G-proteins, Rac1, cdc42 and RhoA in a panel of five human tumor cell lines under normoxic and hypoxic conditions...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28559303/trpc1-is-a-differential-regulator-of-hypoxia-mediated-events-and-akt-signaling-in-pten-deficient-breast-cancer-cells
#20
Iman Azimi, Michael J G Milevskiy, Elke Kaemmerer, Dane Turner, Kunsala T D S Yapa, Melissa A Brown, Erik W Thompson, Sarah J Roberts-Thomson, Gregory R Monteith
Hypoxia is a feature of the tumour microenvironment and promotes invasiveness, resistance to chemotherapeutics and cell survival. Our studies identify the transient receptor potential canonical-1 (TRPC1) ion channel as a key component of responses to hypoxia in breast cancer cells. This regulation includes control of specific epithelial to mesenchymal transition (EMT) events and hypoxia-mediated activation of signaling pathways such as activation of the EGFR, STAT3 and the autophagy marker LC3B, through hypoxia-inducible factor-1alpha (HIF1α)-dependent and -independent mechanisms...
May 30, 2017: Journal of Cell Science
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