PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 22(1), P. 173 - 173

Published: Dec. 26, 2020

Breast cancer is a serious health problem worldwide, representing the second cause of death through malignancies among women in developed countries. Population, endogenous and exogenous hormones, physiological, genetic breast-related factors are involved breast pathogenesis. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) signaling pathway cell proliferation, survival, invasion, migration, apoptosis, glucose metabolism DNA repair. In tumors, PIK3CA somatic mutations have been reported, located exon 9 20. Up to 40% estrogen receptor (ER) positive human epidermal growth factor 2 (HER2) -negative primary metastatic cancer. HER2 overexpressed 20–30% cancers. HER1, HER2, HER3 HER4 membrane tyrosine kinases HER which various ligands can be attached, leading PI3K/AKT activation. Currently, clinical studies evaluate inhibitors PI3K/AKT/mTOR axis. main purpose this review present general aspects cancer, components AKT pathway, that activate protein B, PI3K/AKT-breast mutations, PI3K/AKT/mTOR-inhibitors, relationship between everolimus, temsirolimus endocrine therapy.

Language: Английский

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Lipid signalling in plant responses to abiotic stress

Plant Cell & Environment, Journal Year: 2015, Volume and Issue: 39(5), P. 1029 - 1048

Published: Oct. 29, 2015

Abstract Lipids are one of the major components biological membranes including plasma membrane, which is interface between cell and environment. It has become clear that membrane lipids also serve as substrates for generation numerous signalling such phosphatidic acid, phosphoinositides, sphingolipids, lysophospholipids, oxylipins, N ‐acylethanolamines, free fatty acids others. The enzymatic production metabolism these molecules tightly regulated can rapidly be activated upon abiotic stress signals. Abiotic like water deficit temperature triggers lipid‐dependent cascades, control expression gene clusters activate plant adaptation processes. Signalling able to recruit protein targets transiently thus affect conformation activity intracellular proteins metabolites. In plants, knowledge still scarce lipid their physiological consequences. This review focuses on involvement in response stress. We describe lipid‐binding context changing environmental conditions compare different approaches determine lipid–protein interactions, crucial deciphering cascades.

Language: Английский

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The functional universe of membrane contact sites

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(1), P. 7 - 24

Published: Nov. 15, 2019

Language: Английский

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Plant cell-surface GIPC sphingolipids sense salt to trigger Ca2+ influx

Nature, Journal Year: 2019, Volume and Issue: 572(7769), P. 341 - 346

Published: July 31, 2019

Language: Английский

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PI3K isoforms in cell signalling and vesicle trafficking

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(9), P. 515 - 534

Published: May 20, 2019

Language: Английский

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Quantitative analysis of mammalian GIRK2 channel regulation by G proteins, the signaling lipid PIP2 and Na+ in a reconstituted system

eLife, Journal Year: 2014, Volume and Issue: 3

Published: July 20, 2014

GIRK channels control spike frequency in atrial pacemaker cells and inhibitory potentials neurons. By directly responding to G proteins, PIP2 Na(+), is under the of multiple signaling pathways. In this study, mammalian GIRK2 channel has been purified reconstituted planar lipid membranes effects Gα, Gβγ, Na(+) analyzed. Gβγ must be present simultaneously activate GIRK2. not essential but modulates effect over physiological concentrations. Gαi1(GTPγS) no effect, whereas Gαi1(GDP) closes through removal Gβγ. presence opens as a function mole fraction with Hill coefficient 2.5 an affinity that poises respond natural variations concentration. The dual requirement for can help explain why activated by Gi/o, Gq coupled GPCRs.

Language: Английский

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A novel probe for phosphatidylinositol 4-phosphate reveals multiple pools beyond the Golgi

The Journal of Cell Biology, Journal Year: 2014, Volume and Issue: 205(1), P. 113 - 126

Published: April 7, 2014

Polyphosphoinositides are an important class of lipid that recruit specific effector proteins to organelle membranes. One member, phosphatidylinositol 4-phosphate (PtdIns4P) has been localized Golgi membranes based on the distribution binding modules from PtdIns4P proteins. However, these probes may be biased by additional interactions with other Golgi-specific determinants. In this paper, we derive a new biosensor using SidM (P4M) domain secreted protein bacterial pathogen Legionella pneumophila. was necessary and sufficient for localization P4M, which revealed pools associated not only but also plasma membrane Rab7-positive late endosomes/lysosomes. determined activities both its anabolic catabolic enzymes. Therefore, P4M reports wider cellular than previous therefore will valuable dissecting biological functions in assorted compartments.

Language: Английский

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A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malaria parasites

Science, Journal Year: 2020, Volume and Issue: 367(6473), P. 51 - 59

Published: Jan. 3, 2020

Artemisinin and its derivatives (ARTs) are the frontline drugs against malaria, but resistance is jeopardizing their effectiveness. ART mediated by mutations in parasite's Kelch13 protein, function role remain unclear. In this study, we identified proteins located at a Kelch13-defined compartment. Inactivation of eight these proteins, including Kelch13, rendered parasites resistant to ART, revealing pathway critical for resistance. Functional analysis showed that required endocytosis hemoglobin from host cell. Parasites with inactivated or resistance-conferring mutation displayed reduced endocytosis. ARTs activated degradation products hemoglobin. Hence, activity interactors diminishes thereby activation, resulting parasite

Language: Английский

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Phosphoinositides regulate ion channels

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2014, Volume and Issue: 1851(6), P. 844 - 856

Published: Sept. 18, 2014

Language: Английский

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Endoplasmic Reticulum–Plasma Membrane Contact Sites

Annual Review of Biochemistry, Journal Year: 2017, Volume and Issue: 86(1), P. 659 - 684

Published: March 16, 2017

The endoplasmic reticulum (ER) has a broad localization throughout the cell and forms direct physical contacts with all other classes of membranous organelles, including plasma membrane (PM). A number protein tethers that mediate these have been identified, study revealed multiplicity roles in physiology, regulation intracellular Ca 2+ dynamics signaling as well control lipid traffic homeostasis. In this review, we discuss cross talk between ER PM mediated by contacts. We review factors tether two membranes, their properties, response to functional state cell. focus particular on role ER–PM nonvesicular transport bilayers transfer proteins.

Language: Английский

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