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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Mechanisms of estrogen signaling and gene expression via GPR30

Molecular and Cellular Endocrinology, Journal Year: 2009, Volume and Issue: 308(1-2), P. 32 - 38

Published: April 16, 2009

Language: Английский

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Uveal melanoma: epidemiology, etiology, and treatment of primary disease

Clinical ophthalmology, Journal Year: 2017, Volume and Issue: Volume 11, P. 279 - 289

Published: Jan. 1, 2017

Uveal melanoma: epidemiology, etiology, and treatment of primary disease Benjamin A Krantz,1 Nikita Dave,2 Kimberly M Komatsubara,2 Brian P Marr,3,4 Richard D Carvajal5 1Division Hospital Medicine, 2Division Hematology/Oncology, Columbia University Medical Center, 3Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer 4Department Ophthalmology, Weill Cornell College, 5Division New York, NY, USA Abstract: melanoma (UM) is the most common intraocular malignancy arises from melanocytes in iris, ciliary body, or choroid. Early diagnosis local crucial, as survival correlates with tumor size. However, approximately 50% patients will develop metastatic 6–12 months’ diagnosis. Genomic analyses have led to development gene-expression profiles that effectively predict progression; unfortunately, no adjuvant therapy has been shown prolong date. insights into molecular biology UM found frequent activating mutations genes encoding for G-protein α-subunit, GNAQ GNA11, improved understanding downstream signaling pathways MAPK, PI3K/Akt, Hippo afforded an array new targets this disease. Studies are under way rationally developed regimens targeting these pathways, novel agents development. We review diagnosis, management, surveillance trials way. Keywords: uveal melanoma, ocular GNAQ, MAP kinase, MEK

Language: Английский

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Protein kinase C controls lysosome biogenesis independently of mTORC1

Nature Cell Biology, Journal Year: 2016, Volume and Issue: 18(10), P. 1065 - 1077

Published: Sept. 12, 2016

Language: Английский

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The many faces of calmodulin in cell proliferation, programmed cell death, autophagy, and cancer

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2013, Volume and Issue: 1843(2), P. 398 - 435

Published: Nov. 2, 2013

Language: Английский

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Metformin Disrupts Crosstalk between G Protein–Coupled Receptor and Insulin Receptor Signaling Systems and Inhibits Pancreatic Cancer Growth

Cancer Research, Journal Year: 2009, Volume and Issue: 69(16), P. 6539 - 6545

Published: Aug. 12, 2009

Abstract Recently, we identified a novel crosstalk between insulin and G protein–coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells. Insulin enhanced GPCR through rapamycin-sensitive mTOR-dependent pathway. Metformin, the most widely used drug treatment of type 2 diabetes, activates AMP kinase (AMPK), which negatively regulates mTOR. Here, determined whether metformin disrupts Treatment cells (PANC-1, MIAPaCa-2, BxPC-3) with (10 ng/mL) for 5 minutes markedly increase intracellular [Ca2+] induced by agonists (e.g., neurotensin, bradykinin, angiotensin II). Metformin pretreatment completely abrogated insulin-induced potentiation Ca2+ but did not interfere effect alone. also agonist–induced growth, measured DNA synthesis, number cultured adherent or nonadherent conditions. Low doses (0.1–0.5 mmol/L) blocked stimulation anchorage-dependent anchorage-independent growth agonists. striking sustained phosphorylation AMPK at Thr172 selective inhibitor (compound C, μmol/L) reversed effects on [Ca2+]i indicating that acts activation. In view these results, tested inhibits growth. Administration significantly decreased MIAPaCa-2 PANC-1 xenografted flank nude mice. These results raise possibility could be potential candidate strategies cancer. [Cancer Res 2009;69(16):6539–45]

Language: Английский

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Prostaglandins in bone: bad cop, good cop?

Trends in Endocrinology and Metabolism, Journal Year: 2010, Volume and Issue: 21(5), P. 294 - 301

Published: Jan. 15, 2010

Language: Английский

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The Role of Src Kinase in Macrophage-Mediated Inflammatory Responses

Mediators of Inflammation, Journal Year: 2012, Volume and Issue: 2012, P. 1 - 18

Published: Jan. 1, 2012

Src kinase (Src) is a tyrosine protein that regulates cellular metabolism, survival, and proliferation. Many studies have shown plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, induction migration, which strongly implies pivotal role functional activation macrophages. Macrophages are involved variety immune responses diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, osteoporosis. Previous suggested for responses; however, recently, new functions been reported, implying not described. In this paper, we discuss recent regarding number these newly defined responses. Moreover, feasibility target development pharmaceutical drugs to treat diseases. We provide insights into reports related macrophage-related novel inhibitors with strong immunosuppressive anti-inflammatory properties, could be applied various

Language: Английский

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Suppression of Feedback Loops Mediated by PI3K/mTOR Induces Multiple Overactivation of Compensatory Pathways: An Unintended Consequence Leading to Drug Resistance

Molecular Cancer Therapeutics, Journal Year: 2014, Volume and Issue: 13(11), P. 2477 - 2488

Published: Oct. 17, 2014

The development of drug resistance by cancer cells is recognized as a major cause for failure and disease progression. PI3K/AKT/mTOR pathway aberrantly stimulated in many thus it has emerged target therapy. However, mTORC1 S6K also mediate potent negative feedback loops that attenuate signaling via insulin/insulin growth factor receptor other tyrosine kinase receptors. Suppression these causes overactivation upstream pathways, including PI3K, AKT, ERK potentially oppose the antiproliferative effects mTOR inhibitors lead to resistance. A corollary this concept release consequent compensatory promitogenic pathways response signal can circumvent mitogenic block imposed targeting only one pathway. Consequently, elucidation regulate outputs networks an area fundamental importance rational design effective anticancer combinations inhibitors. Here, we review undergo suppress inhibition underscore unintended activation clinically relevant mTOR, or PI3K/mTOR.

Language: Английский

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Pancreatogenic Diabetes: Special Considerations for Management

Pancreatology, Journal Year: 2011, Volume and Issue: 11(3), P. 279 - 294

Published: July 11, 2011

Language: Английский

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