Journal ArticleDOI
Endothelin 1 in cancer: biological implications and therapeutic opportunities.
TLDR
The advances in the understanding of the diverse biological roles of ET1 are discussed and the latest preclinical and clinical progress that has been made using small-molecule antagonists ofET1 receptors that inhibit ET1-driven signalling are described.Abstract:
Activation of autocrine and paracrine signalling by endothelin 1 (ET1) binding to its receptors elicits pleiotropic effects on tumour cells and on the host microenvironment. This activation modulates cell proliferation, apoptosis, migration, epithelial-to-mesenchymal transition, chemoresistance and neovascularization, thus providing a strong rationale for targeting ET1 receptors in cancer. In this Review, we discuss the advances in our understanding of the diverse biological roles of ET1 in cancer and describe the latest preclinical and clinical progress that has been made using small-molecule antagonists of ET1 receptors that inhibit ET1-driven signalling.read more
Citations
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The Microenvironmental Landscape of Brain Tumors
TL;DR: A number of distinct features of the brain tumor microenvironment are discussed, including brain-resident cell types, the blood-brain barrier, and various aspects of the immune-suppressive environment.
Journal ArticleDOI
Melatonin for the prevention and treatment of cancer
TL;DR: Melatonin could be an excellent candidate for the prevention and treatment of several cancers, such as breast cancer, prostate cancer, gastric cancer and colorectal cancer, and special attention was paid to the mechanisms of action.
Journal ArticleDOI
Targeting the tumor vasculature to enhance T cell activity.
TL;DR: Tumor vascular targeting synergizes with active and adoptive immunotherapies and normalization of the tumor endothelial barrier enhances T cell infiltration and activity.
Journal ArticleDOI
G Protein-Coupled Receptors in Cancer
Rachel Bar-Shavit,Myriam Maoz,Arun Kancharla,Jeetendra Kumar Nag,Daniel Agranovich,Sorina Grisaru-Granovsky,Beatrice Uziely +6 more
TL;DR: Deciding the appropriate context-dependent conformation of a functional GPCR as well as the contribution of G PCR alterations to cancer development remain significant challenges for the discovery of dominant cancer genes and the development of targeted therapeutics.
Journal ArticleDOI
Endothelins in cardiovascular biology and therapeutics.
Neeraj Dhaun,David J. Webb +1 more
TL;DR: Endothelin 1 is the most potent vasoconstrictor in the human cardiovascular system and contributes to basal vascular tone as well as a number of diseases, such as hypertension, chronic kidney disease, pulmonary arterial hypertension, PAH and pre-eclampsia.
References
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Masashi Yanagisawa,Hiroki Kurihara,Hiroki Kurihara,Sadao Kimura,Yoko Tomobe,Mieko Kobayashi,Youji Mitsui,Yoshio Yazaki,Katsutoshi Goto,Tomoh Masaki +9 more
TL;DR: Cloning and sequencing of preproendothelin complementary DNA shows that mature endothelin is generated through an unusual proteolytic processing, and regional homologies to a group of neurotoxins suggest that endothelins is an endogenous modulator of voltage-dependent ion channels.
Journal ArticleDOI
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
Journal ArticleDOI
Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
TL;DR: Owing to the importance of these tumour-associated phenotypes in metastasis and cancer-related mortality, targeting the products of such cellular plasticity is an attractive but challenging approach that is likely to lead to improved clinical management of cancer patients.
Journal ArticleDOI
Molecular classification of cutaneous malignant melanoma by gene expression profiling
M. Bittner,Paul S. Meltzer,Yi Chen,Yong-hui Jiang,E. A. Seftor,Mary J.C. Hendrix,Michael D. Radmacher,Richard M. Simon,Zohar Yakhini,Amir Ben-Dor,Amir Ben-Dor,Nick Sampas,Edward R. Dougherty,Ena Wang,Francesco M. Marincola,C. Gooden,John Lueders,Arthur A. Glatfelter,P.C.A. Pollock,John D. Carpten,E. Gillanders,D. Leja,K. Dietrich,Christian Beaudry,Michael E. Berens,David S. Alberts,Vernon K. Sondak,Nicholas K. Hayward,J.M. Trent +28 more
TL;DR: Many genes underlying the classification of this subset of melanomas are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas.
Journal ArticleDOI
Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors
TL;DR: It is reported here that the epidermal growth factor receptor (EGFR) and the neu oncoprotein become rapidly tyrosine-phosphorylated upon stimulation of Rat-1 cells with the GPCR agonists endothelin-1, lysophosphatic acid and thrombin, suggesting that there is an intracellular mechanism for transactivation.