Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition

Cancer Research
Natividad R FuentesR S Chapkin

Abstract

Ras signaling originates from transient nanoscale compartmentalized regions of the plasma membrane composed of specific proteins and lipids. The highly specific lipid composition of these nanodomains, termed nanoclusters, facilitates effector recruitment and therefore influences signal transduction. This suggests that Ras nanocluster proteolipid composition could represent a novel target for future chemoprevention interventions. There is evidence that consumption of fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) may reduce colon cancer risk in humans, yet the mechanism underlying this effect is unknown. Here, we demonstrate that dietary n-3 PUFA reduce the lateral segregation of cholesterol-dependent and -independent nanoclusters, suppressing phosphatidic acid-dependent oncogenic KRas effector interactions, via their physical incorporation into plasma membrane phospholipids. This results in attenuation of oncogenic Ras-driven colonic hyperproliferation in both Drosophila and murine models. These findings demonstrate the unique properties of dietary n-3 PUFA in the shaping of Ras nanoscale proteo...Continue Reading

References

Apr 18, 2001·Methods in Enzymology·G G HabetsG Bollag
Jan 2, 2003·Nature Reviews. Cancer·Julian Downward
Jan 16, 2003·The Journal of Cell Biology·Ian A PriorJohn F Hancock
Feb 13, 2003·Current Opinion in Structural Biology·Christian Herrmann
May 29, 2003·The Journal of Nutrition·Yang-Yi FanRobert S Chapkin
Apr 16, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·David W L MaRobert S Chapkin
Feb 14, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jeongmin SeoRobert S Chapkin
May 24, 2007·Methods in Cell Biology·Ching-Wei ChangMary-Ann Mycek
Jul 10, 2007·Nature Cell Biology·Tianhai TianJohn F Hancock
Oct 19, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shannon Reagan-ShawNihal Ahmad
Dec 11, 2007·Biochimica Et Biophysica Acta·Robert S ChapkinIan A Prior
May 17, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Megan N HallJing Ma
Sep 12, 2008·Molecular Biology of the Cell·Kerry InderJohn F Hancock
Oct 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wooki KimRobert S Chapkin
Jun 9, 2009·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Eric L Lien
Feb 24, 2010·Progress in Lipid Research·Wooki KimRobert S Chapkin
Jul 27, 2010·Journal of Lipid Research·Li Rong ShenJing X Kang
Nov 8, 2011·Cell Stem Cell·Benoit BiteauHeinrich Jasper
May 17, 2012·Cancer Research·Ian A PriorCarla Mattos
Jul 5, 2012·PloS One·Harmony F TurkRobert S Chapkin
Aug 7, 2012·Molecular Systems Biology·Maria CarvalhoAndrej Shevchenko
Feb 20, 2013·Small GTPases·Kwang-Jin Cho, John F Hancock
Nov 19, 2013·Nature Methods·Matthew D W PiperLinda Partridge
Dec 25, 2013·Molecular and Cellular Biology·Yong ZhouJohn F Hancock
Feb 26, 2014·The Journal of Cell Biology·Nicholas AriottiRobert G Parton
Mar 22, 2014·Cancer Cell·Andrew G StephenFrank McCormick
Sep 23, 2014·Biochimica Et Biophysica Acta·Yong Zhou, John F Hancock
Oct 18, 2014·Nature Reviews. Drug Discovery·Adrienne D CoxChanning J Der
Jul 17, 2015·Journal of Lipid Research·Carsten SkarkeGarret A FitzGerald
Mar 15, 2016·Oncogene·A K NajumudeenD Abankwa
Apr 28, 2016·Biophysical Journal·Kandice R LeventalIlya Levental
Mar 28, 2017·Biochimica Et Biophysica Acta. Biomembranes·Natividad R FuentesRobert S Chapkin
Mar 31, 2017·Nature Reviews. Molecular Cell Biology·Erdinc SezginChristian Eggeling
Nov 10, 2017·Traffic·Yong Zhou, John F Hancock

❮ Previous
Next ❯

Citations

Mar 16, 2019·Carcinogenesis·Ingrid ElisiaGerald Krystal
Feb 2, 2020·Digestive Diseases and Sciences·Robert S ChapkinJohanna W Lampe
Oct 22, 2019·Biophysical Journal·Michael L SalinasRobert S Chapkin
Aug 14, 2021·Tropical Animal Health and Production·Ícaro Rainyer Rodrigues de CastroKaliandra Souza Alves

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.