3D Culture Models with CRISPR Screens Reveal Hyperactive NRF2 as a Prerequisite for Spheroid Formation via Regulation of Proliferation and Ferroptosis…
Posted: November 3, 2020 at 1:58 am
This article was originally published here
Mol Cell. 2020 Oct 26:S1097-2765(20)30693-6. doi: 10.1016/j.molcel.2020.10.010. Online ahead of print.
ABSTRACT
Cancer-associated mutations that stabilize NRF2, an oxidant defense transcription factor, are predicted to promote tumor development. Here, utilizing 3D cancer spheroid models coupled with CRISPR-Cas9 screens, we investigate the molecular pathogenesis mediated by NRF2 hyperactivation. NRF2 hyperactivation was necessary for proliferation and survival in lung tumor spheroids. Antioxidant treatment rescued survival but not proliferation, suggesting the presence of distinct mechanisms. CRISPR screens revealed that spheroids are differentially dependent on the mammalian target of rapamycin (mTOR) for proliferation and the lipid peroxidase GPX4 for protection from ferroptosis of inner, matrix-deprived cells. Ferroptosis inhibitors blocked death from NRF2 downregulation, demonstrating a critical role of NRF2 in protecting matrix-deprived cells from ferroptosis. Interestingly, proteomics analyses show global enrichment of selenoproteins, including GPX4, by NRF2 downregulation, and targeting NRF2 and GPX4 killed spheroids overall. These results illustrate the value of spheroid culture in revealing environmental or spatial differential dependencies on NRF2 and reveal exploitable vulnerabilities of NRF2-hyperactivated tumors.
PMID:33128871 | DOI:10.1016/j.molcel.2020.10.010
- Natural CRISPR's Safety Feature Could Become Genetic Dimmer Switch - Genetic Engineering & Biotechnology News - January 23rd, 2021
- CRISPR (CRSP) Up More Than 80% in Past 3 Months: Here's Why - Yahoo Finance - January 23rd, 2021
- The Zacks Analyst Blog Highlights: CRISPR Therapeutics, Vertex Pharmaceuticals and Intellia Therapeutics - Yahoo Finance - January 23rd, 2021
- Investors Who Bought CRISPR Therapeutics (NASDAQ:CRSP) Shares Three Years Ago Are Now Up 411% - Simply Wall St - January 23rd, 2021
- We may have a CRISPR cure for red blood diseases sickle cell anemia and beta thalassemia - Genetic Literacy Project - January 23rd, 2021
- The ARKG ETF: Join the Genomics Revolution - ETF Trends - January 23rd, 2021
- Gene-edited crops are now a reality but will the public be on board? - The Conversation UK - January 23rd, 2021
- 'Incredible' gene-editing result in mice inspires plans to treat premature-aging syndrome in children - Science Magazine - January 9th, 2021
- CRISPR Therapeutics Is Still Looking Strong - RealMoney - RealMoney - January 9th, 2021
- Global CRISPR Technology Market Report 2020: COVID-19 Growth and Change - Market is Expected to Recover to Reach $1.55 Billion in 2023 - Forecast to... - January 9th, 2021
- What is the Market's View on Crispr Therapeutics AG (CRSP) Stock's Price and Volume Trends - InvestorsObserver - January 9th, 2021
- 5 questions facing gene therapy in 2021 - BioPharma Dive - January 9th, 2021
- CRISPR-based strategies in infectious disease diagnosis and therapy - DocWire News - January 9th, 2021
- Plant Breeding And CRISPR Plants Market Is Expected To Reach USD 21.78 Billion By 2027 | Top Companies- Bayer AG, KWS SAAT SE & Co. KGaA, DuPont,... - January 9th, 2021
- Where Does Crispr Therapeutics AG (CRSP) Stock Fall in the Biotechnology Field? - InvestorsObserver - January 9th, 2021
- CRISPR and CAS Gene Market 2021-2028 shooting revenue at US$ 7,603.8 Million with CRISPR Therapeutics, Mirus Bio, Caribou Biosciences, Editas... - January 9th, 2021
- The 221b Foundation Establishes Coalition to Control the Spread of COVID-19 in Nepal - Business Wire - January 9th, 2021
- Strategies and applications for CRISPRko, RNAi and beyond - SelectScience - January 9th, 2021
- TRIM26 is a critical host factor for HCV replication and contributes to host tropism - Science Advances - January 9th, 2021
- Four Predictions for the Future of Food in 2021 - The Spoon - January 9th, 2021
- Why CRISPR Therapeutics, Editas Medicine, and Intellia Therapeutics Stocks Are Sinking Today - The Motley Fool - January 2nd, 2021
- Should Crispr Therapeutics AG (CRSP) be in Your Portfolio? - InvestorsObserver - January 2nd, 2021
- Can CRISPR Save Florida Citrus? - AG INFORMATION NETWORK OF THE WEST - AGInfo Ag Information Network Of The West - January 2nd, 2021
- 2020: The year science took centre-stage - The Hindu - January 2nd, 2021
- 2020 was a tough year, but there is a silver lining - Boston Herald - January 2nd, 2021
- Pairing CRISPR with a smartphone camera, this COVID-19 test finds results in 30 minutes - FierceBiotech - December 12th, 2020
- New CRISPR-based COVID-19 test uses smartphone cameras to spot virus RNA - University of California - December 12th, 2020
- Is CRISPR Therapeutics Heading for $170? - The Motley Fool - December 12th, 2020
- Intellia Therapeutics Achieves Normal Human Alpha-1 Antitrypsin Protein Levels in Non-Human Primates Through Targeted Gene Insertion for the Treatment... - December 12th, 2020
- De-extinction: Why CRISPR gene editing might be the most revolutionary development in science ever - Genetic Literacy Project - December 12th, 2020
- How CRISPR could help us discover and treat rare cancers - ZME Science - December 12th, 2020
- ASH: CRISPR-Cas9 Gene Editing Promising in TDT, SCD - HealthDay News - December 12th, 2020
- Kevin Davies' 'Editing Humanity' explores the CRISPR revolution and the ethical dilemmas that await us - Genetic Literacy Project - December 12th, 2020
- ASH 2020: Gilead eyes new Yescarta indication, Vertex/CRISPR make headway in sickle cell and more - PMLiVE - December 12th, 2020
- CiBER-seq dissects genetic networks by quantitative CRISPRi profiling of expression phenotypes - Science Magazine - December 12th, 2020
- CRISPR Therapeutics to Participate in the Piper Sandler 32nd Annual Virtual Healthcare Conference - Yahoo Finance - November 30th, 2020
- Global $6.7 Billion CRISPR Technology Market Opportunities to 2030: Cas9 And gRNA, Design Tool, Plasmid and Vector, Other Delivery System Products -... - November 30th, 2020
- CRISPR Therapeutics AG [CRSP] Revenue clocked in at $77.40 million, up 99.57% YTD: Whats Next? - The DBT News - November 30th, 2020
- Crispr And Crispr-Associated (Cas) Genes Market trends, Forecast Analysis, Key segmentation by type and application to 2026 - Cheshire Media - November 30th, 2020
- CRISPR And CRISPR-Associated (Cas) Genes Market Competitive Insights with Global Outlook 2020-2026| Caribou Biosciences, Addgene, CRISPR THERAPEUTICS... - November 30th, 2020
- CRISPR Genome Editing Market Statistics and Research Analysis Released in Latest Industry Report 2020 | Coronavirus-COVID19 Impact Analysis With Top... - November 30th, 2020
- CRISPR Genome Editing Market to Exhibit Impressive Growth of CAGR during the pe - News by aeresearch - November 30th, 2020
- Autism genes affect development of neurons and glia - Spectrum - November 30th, 2020
- CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy - Science Advances - November 20th, 2020
- Heres Why You Should Stay Invested In CRISPR Stock Despite The Recent 3x Rally - Forbes - November 20th, 2020
- CRISPR for Citrus Greening - AG INFORMATION NETWORK OF THE WEST - AGInfo Ag Information Network Of The West - November 20th, 2020
- CRISPR Therapeutics to Participate in the Jefferies Virtual London Healthcare Conference - Yahoo Finance - November 20th, 2020
- Viewpoint: Farming one of the 'most inefficient industries.' The CRISPR revolution could change that - Genetic Literacy Project - November 20th, 2020
- CRISPR-edited bananas immune to killer pathogens advance toward commercialization in Africa - Genetic Literacy Project - November 20th, 2020
- CRISPR Technology Market Forecast To 2026 And COVID-19 Impact Analysis - The Think Curiouser - November 20th, 2020
- Faster, Cheaper, Easier COVID-19 Testing - Powering the New Engineer - University of Florida - November 20th, 2020
- Seeing Real-Time Biological Interactions with Graphene Transistors - Clinical OMICs News - November 20th, 2020
- Crispr Technology Market to 2026: Report on Top Company Players, Industry Insights and Overview - PRnews Leader - November 20th, 2020
- Application and Product Portfolio Analysis During the forecasted period of CRISPR Technology Market - PRnews Leader - November 20th, 2020
- CRISPR Genome Editing Market Research Report- Opportunities & Challenges With Totally Different Segments, Forecast- 2026 - The Think Curiouser - November 3rd, 2020
- Latest News 2020: CRISPR Technology Market by Coronavirus-COVID19 Impact Analysis With Top Manufacturers Analysis | Top Players: Thermo Fisher... - November 3rd, 2020
- Global CRISPR And CRISPR-Associated (Cas) Genes Market Views: Taking A Nimble Approach To Explores Huge Growth In Near Future With Eminent Players -... - November 3rd, 2020
- The Impact of the Coronavirus on the Global CRISPR and Cas Genes Market Fact.MR Study 2020 2026 - The Cloud Tribune - November 3rd, 2020
- CRISPR And CRISPR-Associated (Cas) Genes Market: Drivers, Restraints, Opportunities, and Threats (20192025) - Eurowire - October 31st, 2020
- CRISPR Can be a Solution to Address the COVID-19 Pandemic | Roots Analysis - The Think Curiouser - October 31st, 2020
- Picking up where GMOs left off: CRISPR leads the way to 'greener' food production in the 21st century - Genetic Literacy Project - October 31st, 2020
- CRISPR is going to reshape the future of probiotic genomes: Expert - NutraIngredients-usa.com - October 29th, 2020
- Did The Underlying Business Drive CRISPR Therapeutics' (NASDAQ:CRSP) Lovely 407% Share Price Gain? - Yahoo Finance - October 29th, 2020
- CRISPR Therapeutics Stock Falls 3.5% on Q3 Results - Motley Fool - October 29th, 2020
- Plant Breeding and CRISPR Plants Market Report 2026 Focuses on Top Companies, Research Methodology, Drivers and Opportunities - Eurowire - October 29th, 2020
- CRISPR pioneer: "Science is on the ballot" in 2020 - Axios - October 28th, 2020
- Fast, cheap, accurate: Researchers pin hopes on Nobel Prize-winning CRISPR technology to detect coronavirus - USA TODAY - October 28th, 2020
- Kara Swisher and Dr. Jennifer Doudna on CRISPR and Its Possibilities - The New York Times - October 28th, 2020
- CRISPR-Cas9: The gene editing tool that has revolutionized molecular biology - McGill Tribune - October 28th, 2020
- Is CRISPR gene therapy for rare Angelman Syndrome on the horizon? - Health Europa - October 28th, 2020
- Molecular Dynamics Reveals a DNA-Induced Dynamic Switch Triggering Activation of CRISPR-Cas12a - DocWire News - October 28th, 2020
- Is CRISPR Therapeutics Really Headed to $110? - Motley Fool - October 28th, 2020
- Investing in Genomics and CRISPR - Everything You Need to Know - Securities.io - October 28th, 2020
- Pac-Man meets genetics in new DNA editing that plays like the game - SYFY WIRE - October 28th, 2020
- CRISPR Technology Market SWOT Analysis, Latest Trends, By Top Key Players- Thermo Fisher Scientific Merck KGaA GenScript Integrated DNA Technologies... - October 28th, 2020
- Women in Science: Thoughts on the 2020 Nobel Prize in Chemistry - Loma Beat - October 28th, 2020
- CRISPR Technology Market Will Generate New Growth Opportunities in the upcoming year - Aerospace Journal - October 28th, 2020
- CRISPR and Cas Genes Market Insight | Strategic Industry Evolutionary Analysis Focus on Leading Key Players and Revenue Growth Analysis by Forecast To... - October 28th, 2020
- CRISPR Technology Market 2020: Potential growth, attractive valuation make it is a long-term investment | Know the COVID19 Impact | Top Players:... - October 28th, 2020
- 'CRISPR and Coronavirus': Hear From Nobel Winner Jennifer Doudna - UC Davis - October 22nd, 2020