Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing

Cell, Journal Year: 2012, Volume and Issue: 150(6), P. 1107 - 1120

Published: Sept. 1, 2012

Language: Английский

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The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation

Trends in Biochemical Sciences, Journal Year: 2011, Volume and Issue: 36(6), P. 320 - 328

Published: May 3, 2011

Language: Английский

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Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways

Cancers, Journal Year: 2017, Volume and Issue: 9(5), P. 52 - 52

Published: May 17, 2017

The epidermal growth factor receptor (EGFR) is a tyrosine kinase that commonly upregulated in cancers such as non-small-cell lung cancer, metastatic colorectal glioblastoma, head and neck pancreatic breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations truncations to its extracellular domain, EGFRvIII truncations, well L858R T790M mutations, or exon 19 truncation. These aberrations over-activate downstream pro-oncogenic signaling pathways, RAS-RAF-MEK-ERK MAPK AKT-PI3K-mTOR pathways. pathways then activate many biological outputs are beneficial cancer cell proliferation, their chronic initiation progression through cycle. Here, we review molecular regulate signal transduction, structure ligand binding dimerization, lead G1 cycle progression. We focus on induction CYCLIN D expression, CDK4/6 activation, repression cyclin-dependent inhibitor proteins (CDKi) by also discuss successes challenges EGFR-targeted therapies, potential for use combination with inhibitors.

Language: Английский

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Mechanisms of Hippo pathway regulation

Genes & Development, Journal Year: 2016, Volume and Issue: 30(1), P. 1 - 17

Published: Jan. 1, 2016

The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied both mammals the last several years. core of consists kinase cascade, transcription coactivators, DNA-binding partners. Recent studies have expanded as complex signaling network with >30 components. This is regulated by intrinsic cell machineries, such cell–cell contact, polarity, actin cytoskeleton, well wide range signals, including cellular energy status, mechanical cues, hormonal signals that act through G-protein-coupled receptors. major functions defined to restrict adults modulate proliferation, differentiation, migration developing organs. Furthermore, dysregulation leads aberrant neoplasia. In this review, we focus on recent developments our understanding molecular actions cascade discuss key open questions regulation function pathway.

Language: Английский

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Insulin Receptor Signaling in Normal and Insulin-Resistant States

Cold Spring Harbor Perspectives in Biology, Journal Year: 2014, Volume and Issue: 6(1), P. a009191 - a009191

Published: Jan. 1, 2014

Jérémie Boucher1,2, André Kleinridders1,2 and C. Ronald Kahn1 1Section on Integrative Physiology Metabolism, Joslin Diabetes Center Department of Medicine, Brigham Women's Hospital Harvard Medical School, Boston, Massachusetts 02115 Correspondence: c.ronald.kahn{at}joslin.harvard.edu ↵2 These authors contributed equally to this article.

Language: Английский

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The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

International Journal of Molecular Medicine, Journal Year: 2017, Volume and Issue: 40(2), P. 271 - 280

Published: June 22, 2017

Protein phosphorylation is an impo-rtant cellular regulatory mechanism as many enzymes and receptors are activated/deactivated by dephosphorylation events, means of kinases phosph-atases. In particular, the protein responsible for transduction signaling their hyperactivity, malfunction or overexpression can be found in several diseases, mostly tumors. Therefore, it evident that use kinase inhibitors valuable treatment cancer. this review, we discuss action phosphorylation, with particular attention to importance under physiological pathological conditions. We also possibility using

Language: Английский

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PI3K/AKT signaling pathway and cancer: an updated review

Annals of Medicine, Journal Year: 2014, Volume and Issue: 46(6), P. 372 - 383

Published: June 5, 2014

Despite development of novel agents targeting oncogenic pathways, matching targeted therapies to the genetic status individual tumors is proving be a daunting task for clinicians. To improve clinical efficacy and reduce toxic side effects treatments, deep characterization alterations in different required. The mutational profile often evidences gain function or hyperactivity phosphoinositide 3-kinases (PI3Ks) tumors. These enzymes are activated downstream tyrosine kinase receptors (RTKs) and/or G proteins coupled (GPCRs) and, via AKT, able induce mammalian target rapamycin (mTOR) stimulation. Here, we elucidate impact class I (p110α, β, γ, δ) catalytic subunit mutations on AKT-mediated cellular processes that control crucial mechanisms tumor development. Moreover, interrelation PI3K signaling with mTOR, ERK, RAS pathways will discussed, exploiting potential benefits inhibitors use.

Language: Английский

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The mTOR-Regulated Phosphoproteome Reveals a Mechanism of mTORC1-Mediated Inhibition of Growth Factor Signaling

Science, Journal Year: 2011, Volume and Issue: 332(6035), P. 1317 - 1322

Published: June 10, 2011

A search for substrates of a growth-promoting kinase revealed regulatory feedback loop involved in tumor suppression.

Language: Английский

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Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks

Biochemical Journal, Journal Year: 2011, Volume and Issue: 441(1), P. 1 - 21

Published: Dec. 14, 2011

The ribosomal protein S6K (S6 kinase) represents an extensively studied effector of the TORC1 [TOR (target rapamycin) complex 1], which possesses important yet incompletely defined roles in cellular and organismal physiology. functions as environmental sensor by integrating signals derived from diverse cues to promote anabolic inhibit catabolic functions. mTORC1 (mammalian TORC1) phosphorylates activates S6K1 S6K2, whose first identified substrate was rpS6 (ribosomal S6), a component 40S ribosome. Studies over past decade have uncovered number additional substrates, revealing multiple levels at mTORC1–S6K1 axis regulates cell results thus far indicate that controls fundamental processes, including transcription, translation, lipid synthesis, growth/size metabolism. In present review we summarize regulation S6Ks, their substrates functions, integration within rapidly expanding mTOR TOR) signalling networks. Although our understanding role physiology remains its infancy, evidence indicates this controls, least part, glucose homoeostasis, insulin sensitivity, adipocyte metabolism, body mass energy balance, tissue organ size, learning, memory aging. As dysregulation contributes disease states, improved function networks may enable development novel therapeutics.

Language: Английский

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Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2

Diabetologia, Journal Year: 2012, Volume and Issue: 55(10), P. 2565 - 2582

Published: Aug. 6, 2012

Language: Английский

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