The JAK2 Inhibitor AZD1480 Potently Blocks Stat3 Signaling and Oncogenesis in Solid Tumors
Michael Hedvat,Dennis Huszar,Andreas Herrmann,Joseph M. Gozgit,Anne Schroeder,Adam Sheehy,Ralf Buettner,David Proia,Claudia M. Kowolik,Hong Xin,Brian Armstrong,Geraldine Bebernitz,Shaobu Weng,Lin Wang,Minwei Ye,Kristen McEachern,Huawei Chen,Deborah Morosini,Kirsten Bell,Marat Alimzhanov,Stephanos Ioannidis,Patricia McCoon,Zhu A. Cao,Hua Yu,Richard Jove,Michael Zinda +25 more
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TLDR
The essential role of Stat3 downstream of Jaks is demonstrated by inhibition of tumor growth using short hairpin RNA targeting Stat3, supporting a key role of Jak kinase activity in Stat3-dependent tumorigenesis.About:
This article is published in Cancer Cell.The article was published on 2009-12-08 and is currently open access. It has received 512 citations till now. The article focuses on the topics: JAK2 Inhibitor AZD1480 & Janus kinase.read more
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Immunity, Inflammation, and Cancer
TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.
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Natural Innate and Adaptive Immunity to Cancer
Matthew D. Vesely,Michael H. Kershaw,Michael H. Kershaw,Michael H. Kershaw,Robert D. Schreiber,Mark J. Smyth,Mark J. Smyth +6 more
TL;DR: Current experimental and human clinical data supporting a cancer immunoediting process that provide the fundamental basis for further study of immunity to cancer and for the rational design of immunotherapies against cancer are discussed.
Journal ArticleDOI
Targeting the IL-6/JAK/STAT3 signalling axis in cancer.
TL;DR: Treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity.
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NF-κB and STAT3 - key players in liver inflammation and cancer.
Guobin He,Michael Karin +1 more
TL;DR: This review will focus on recent studies on the roles of NF-κB and STAT3 in liver cancer and interactions between the two pathways and their potential as therapeutic targets.
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The JAK2/STAT3 signaling pathway is required for growth of CD44+CD24– stem cell–like breast cancer cells in human tumors
Lauren L. C. Marotta,Vanessa Almendro,Vanessa Almendro,Andriy Marusyk,Michail Shipitsin,Janina Schemme,Sarah R. Walker,Noga Bloushtain-Qimron,Jessica J. Kim,Sibgat Choudhury,Reo Maruyama,Zhenhua Wu,Mithat Gonen,Laura Mulvey,Marina Bessarabova,Sung Jin Huh,Serena J. Silver,So Young Kim,So Young Kim,So Yeon Park,Hee Eun Lee,Karen S. Anderson,Andrea L. Richardson,Tatiana Nikolskaya,Yuri Nikolsky,X. Shirley Liu,David E. Root,William C. Hahn,William C. Hahn,David A. Frank,Kornelia Polyak +30 more
TL;DR: The IL-6/JAK2/Stat3 pathway was preferentially active in CD44+CD24- breast cancer cells compared with other tumor cell types, and inhibition of JAK2 decreased their number and blocked growth of xenografts.
References
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Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
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STATs and Gene Regulation
TL;DR: The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins.
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Stat3 as an Oncogene
Jacqueline Bromberg,Melissa H. Wrzeszczynska,Geeta Devgan,Yanxiang Zhao,Richard G. Pestell,Chris Albanese,James E. Darnell +6 more
TL;DR: Substitution of two cysteine residues within the C-terminal loop of the SH2 domain of Stat3 produces a molecule that dimerizes spontaneously, binds to DNA, and activates transcription.
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The STATs of cancer — new molecular targets come of age
Hua Yu,Richard Jove +1 more
TL;DR: Tumour cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance, and STAT proteins — especially STAT3 and STAT5 — regulate all of these processes and are persistence activated in a surprisingly large number of human cancers.
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IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated Cancer
Sergei I. Grivennikov,Eliad Karin,Janoš Terzić,Janoš Terzić,Daniel Mucida,Guann-Yi Yu,Sivakumar Vallabhapurapu,Jürgen Scheller,Stefan Rose-John,Hilde Cheroutre,Lars Eckmann,Michael Karin +11 more
TL;DR: It is demonstrated that IL-6 is a critical tumor promoter during early CAC tumorigenesis and the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs.