Cancer cells express different genes than normal cells, and these new gene expression patterns are key to cancer behavior. One way cells can alter gene expression is by adding small chemical modifications to the DNA or associated proteins called epigenetic markers that determine which genes are turned on or off.
Take brain tumors, for example. A team led by researchers at Baylor College of Medicine has investigated the genetic regulation of brain tumor behavior. Specifically, they studied Sox9-mediated mechanisms of epigenetic dysregulation in two mouse models of human brain tumors: high-grade glioma (HGG) and ependymoma (EPN).
Sox9, a well-known transcription factor, has emerged as a key regulator of epigenetic modifications and gene expression programs that contribute to brain tumor growth; however, how Sox9 achieves this is not well known, said co-first author Dr. Debosmita Sardar, postdoctoral associate in the lab of Dr. Benjamin Deneen at Baylor.
We knew that Sox9 is elevated in both HGG and EPN. Also, we knew that these tumors have different epigenetic profiles, said co-first author Hsiao-Chi-Eileen-Chen, graduate student in the Deneen lab. We wanted to know whether Sox9 was involved in shaping these distinct profiles and the mechanism that led to them.
We expected that Sox9s contribution to set up the tumors epigenetic patterns would be the same, said Deneen, professor and Dr. Russell J. and Marian K. Blattner Chair of neurosurgery and the Center for Cancer Neuroscience at Baylor. Deneen also is the corresponding author of the work.
The function of a gene, in this case Sox9, is assumed to be the same regardless of the cell type in which the gene is expressed. We found something unexpected in that Sox9 function was dramatically different in these two different tumors.
The researchers manipulated Sox9 expression in the mouse models and found that increasing Sox9 suppressed tumor growth in HGG but promoted it in EPN. Surprisingly, Sox9 regulated the epigenetic patterns of HGG and EPN in different ways. In HGG, Sox9 mediated its effect by interacting with a group of proteins called histone deacetylation complex, while in EPN Sox9 interacted with oncofusion proteins. Sox9 has different protein-protein interactions in different tumors.
This is what is really driving the different ways Sox9 regulates epigenetic patterns in these tumors, Sardar said. Its actions are tumor-specific and we essentially took advantage of state-of-the art proteomic technologies to uncover these distinct mechanisms.
Importantly, we also see these distinct Sox9 protein-protein interactions in human HGG tumor samples graciously provided by Dr. Ganesh Rao, Marc J. Shapiro professor and chair of neurosurgery at Baylor, Chen said. Also, our collaboration with Dr. Stephen Mack at St. Jude Childrens Research Hospital was crucial for comparing epigenetic datasets of our mouse models with clinical tumor samples from human patients.
This revealed a strong overlap between epigenetic profiles in our mouse models and human tumors, establishing these mouse models as powerful tools to understand clinically relevant tumor behaviors. These findings suggest new possibilities for developing novel therapies directed at epigenetic mechanisms.
Looking to read all the details of this work? Find it in Proceedings of the National Academy of Sciences.
Other contributors to this work include Amanda Reyes, Srinidhi Varadharajan, Antrix Jain, Carrie Mohila, Rachel Curry, Brittney Lozzi, Kavitha Rajendran, Alexis Cervantes, Kwanha Yu, Ali Jalali and Ganesh Rao. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Center for Stem Cells and Regenerative Medicine at Baylor, Center for Cancer Neuroscience at Baylor, St. Jude Childrens Research Hospital, University of Houston and Texas Childrens Hospital.
Financial support for this project was provided by grants from the National Institutes of Health (R01-NS071153 to BD, R01-NS124093, R01NS094615, K08-NS110976, 1R01NS116361, 1K99-DC019668, P30 CA125123, S10OD026804), National Cancer Institute-Cancer Therapeutic Discovery (U01-CA217842) and the Diana Helis Henry and Adrienne Helis Malvin Medical Research Foundation. Further support was provided by an ALSF A Award, a CPRIT Scholar in Cancer Research Award, CPRIT Core Facility Award (RP210227), Pediatric Brain Tumor Foundation, V Scholar Foundation and ALSAC St Jude Childrens Research Hospital.
By Ana Mara Rodrguez, Ph.D.
Originally posted here:
Unanticipated findings cast new light on the genetic regulation of different brain tumors - Baylor College of Medicine
- Cardiovascular Glossary A-Z (All) | Texas Heart Institute - January 4th, 2023
- ADC Therapeutics Announces Abstracts to be Presented at the Tenth Annual Meeting of the Society of Hematologic Oncology (SOHO 2022) - Business Wire - September 25th, 2022
- GVHD in the Context of Stem Cell or Allogeneic Transplant - Cancer Network - August 22nd, 2022
- De-extinction Company Aims to Resurrect the Tasmanian Tiger - Scientific American - August 22nd, 2022
- Dean Kamen on the power of celebrating your own obsoletion - TechCrunch - July 27th, 2022
- Westin and Sehn Carve Out the Role of CAR T-Cell Therapy and Transplant in Primary Refractory DLBCL - OncLive - July 27th, 2022
- Chaotic response in Uvalde, Parkland shooter faces death penalty, mall shooting leaves 3 dead and jury selection begins in Bannon trial | Hot off the... - July 19th, 2022
- Stem Cells, Abortion, Baby Parts, & the Ukraine - Physicians for Life - June 22nd, 2022
- INVECTYS, MD ANDERSON AND CTMC ANNOUNCE STRATEGIC COLLABORATION FOR CAR T CELL THERAPY DEVELOPMENT - BioSpace - June 22nd, 2022
- Quizartinib Plus Chemotherapy Significantly Improved Overall Survival Compared to Chemotherapy in Patients with Newly Diagnosed FLT3-ITD Positive... - June 13th, 2022
- Texas Family Fights to Access $2.1 Million Treatment for Baby - NBC 5 Dallas-Fort Worth - May 15th, 2022
- La Conner native raising funds to cure blood cancer - La Conner Weekly News - May 2nd, 2022
- CORRECTING and REPLACING -- Affimed NV - GlobeNewswire - May 2nd, 2022
- StudyFinds Blotter: Other Notable Health Research From April 28, 2022 - Study Finds - May 2nd, 2022
- Sung to lead cancer institute; Bankston wins fellowship - ASBMB Today - April 19th, 2022
- Houston teen first in Texas to become own donor to reverse sickle cell anemia - FOX 26 Houston - March 25th, 2022
- Oleic Acid, a Key to Activating the Brains Fountain of Youth - Neuroscience News - March 25th, 2022
- Stem Cell Therapy Boosts Outcomes for Some Heart Failure Patients - HealthDay - November 22nd, 2021
- Quizartinib Added to Chemotherapy Demonstrates Superior Overall Survival Compared to Chemotherapy Alone in Adult Patients with Newly Diagnosed... - November 22nd, 2021
- BioBridge Global continues history of innovation with umbilical cord collection and processing under cGMP standards for further manufacture - Yahoo... - November 22nd, 2021
- Immatics to Present Update on Lead ACTengine Program IMA203 Targeting PRAME at the Society for Immunotherapy of Cancers 36th Annual Meeting - Yahoo... - November 8th, 2021
- Affimed Announces Poster Presentations at the 63rd American Society of Hematology Annual ... - Tyler Morning Telegraph - November 8th, 2021
- ADC Therapeutics Announces Abstracts to be Presented at the 63rd ASH Annual Meeting - StreetInsider.com - November 8th, 2021
- The Power of the Immune System: New Treatment for Painful Blood Cancer Side Effect - Curetoday.com - October 28th, 2021
- Durham firm offering up to $10,000 for researchers to use its intestinal technology - WRAL Tech Wire - October 16th, 2021
- Elevated cryptic transcription emerges as a common theme in aging mammalian cells - Baylor College of Medicine News - August 31st, 2021
- Insulin-producing implants are being developed to control Type 1 diabetes - Health Europa - August 5th, 2021
- Cryptic Transcription in Mammalian Stem Cells Linked to Aging - Technology Networks - August 5th, 2021
- Overview of DLBCL - Targeted Oncology - August 5th, 2021
- The True Crime Junkies and the Curious Case of a Missing Husband - VICE - August 5th, 2021
- FROM THE LABS: Hispanic Heritage Spotlight: Interview with Dr. Nino Rainusso - Baylor College of Medicine News - November 13th, 2020
- UPMC nurse practitioner hailed 'healthcare hero' on live TV - Altoona Mirror - October 31st, 2020
- BrainStrom Cell Therapeutics (NASDAQ:BCLI) Enters Agreement With Catalent (NYSE:CTLT) For Manufacture Of Its NurOwn Cell Therapy - BP Journal - October 31st, 2020
- Dr. Daisy Ayim, Cosmetic Surgeon, ObGyn, Business Owner and Entrepreneur, Is Revolutionizing The Integration Of Women's Health And Cosmetic Care -... - October 31st, 2020
- Five Indian American Researchers Named Among NIH 2020 New Innovator Awardees - India West - October 21st, 2020
- Reliable tumor detection by whole-genome methylation sequencing of cell-free DNA in cerebrospinal fluid of pediatric medulloblastoma - Science... - October 21st, 2020
- Biotechnology could change the cattle industry. Will it succeed? - Salon - September 8th, 2020
- STEM CELLS | VitaDrip IV Therapy | Texas - June 26th, 2020
- New Preclinical Data Demonstrates Immune-Enhancing Effects of Triple I/O Combination Therapy with BeyondSpring's Plinabulin - BioSpace - June 23rd, 2020
- Tau: Why Alzheimer's Worsens Fast in Some, Slowly in Others - Alzforum - June 23rd, 2020
- Scholarly Perspectives on COVID-19, Part 1: This Was Only a Matter of Time - Southern Newsroom - June 23rd, 2020
- Texas Stem Cell Law Opens Door for Controversial Treatments - June 11th, 2020
- Who's to blame? These three scientists are at the heart of the Surgisphere COVID-19 scandal - Science Magazine - June 9th, 2020
- FTC ramps up enforcement with new wave of warning letters - NutraIngredients-usa.com - June 9th, 2020
- UT Student Awarded Prestigious Astronaut Scholarship - UT News | The University of Texas at Austin - June 9th, 2020
- South Sound Community Bands Together To Save Local Lives - southsoundtalk.com - May 7th, 2020
- Pfizer, NYU working on innovative coronavirus vaccine that could be ready by end of summer - NBC News - May 7th, 2020
- How industry hopes to take on COVID-19 - Bioprocess Insider - BioProcess Insider - March 8th, 2020
- Meng Hsieh, Andrew Shubin - The New York Times - March 8th, 2020
- Jimbo Fisher's Kidz1stFund, Aggie Corps of Cadets team up for Be the Match bone marrow donor registry drive - Bryan-College Station Eagle - March 2nd, 2020
- Texas A&M Researcher Named To National List Of Inspiring Black Scientists - Texas A&M University - March 2nd, 2020
- What to do in Madison: March 2-8, 2020 - The Bozho - March 2nd, 2020
- Cumberland County family turns to non-FDA approved stem cell treatment to help two-year-old son with cerebral palsy - FOX43.com - February 27th, 2020
- Recombinetics Announces Collaboration with University of Texas Southwestern to Advance Regenerative Medicine Through Therapeutic Cell, Tissue, and... - February 27th, 2020
- Stem Cell Therapy for Joints & Spine in Austin Texas - January 28th, 2020
- El Paso scientists to deliver 3D bioprinted miniature hearts to the ISS - 3D Printing Industry - January 28th, 2020
- El Paso scientists team up for heart research project at the International Space Station - KVIA El Paso - January 28th, 2020
- Drugs, Biologics, and Regenerative Medicine in 2019: A Successful Year Ends with Promise of a More Challenging 2020 - JD Supra - December 18th, 2019
- Incoming Faculty Bring New Areas of Research to Rensselaer - Rensselaer Polytechnic Institute - September 24th, 2019
- Nivolumab as an addition to frontline therapy of AML in younger patients - AML Global Portal - September 24th, 2019
- Interview: BIOLIFE4D is The First US Company to Bioprint a Mini-Heart (for Cardiotoxicity Testing) - 3DPrint.com - September 24th, 2019
- Stem cells regrow leg's long bones - WNDU-TV - September 22nd, 2019
- A breakthrough in the battle against citrus greening - Gainesville Sun - September 22nd, 2019
- Comparing Mymetics (OTCMKTS:MYMX) & Crispr Therapeutics (OTCMKTS:CRSP) - TechNewsObserver - September 22nd, 2019
- STEM CELL THERAPY & TREATMENTS Texas Regional Health - September 10th, 2019
- Fast Facts: Stem Cells 101 Vital Record - September 10th, 2019
- Keller, TX Stem Cells | Neuropathy & Pain Centers of Texas - May 31st, 2019
- Arlington Stem Cells | Neuropathy & Pain Centers of Texas - May 1st, 2019
- Houston, Texas Stem Cell Transplants, Richmond, Sugar Land ... - April 21st, 2019
- Fort Worth Stem Cells | Neuropathy and Pain Centers of Texas - April 15th, 2019
- Stem Cell Rejuvenation Therapy | Totalhormonegenetherapy.com - April 15th, 2019
- Our Doctors - Knee Stem Cells - March 17th, 2019
- Stem Cell Treatment Center in Dallas, Texas | Stem Cell ... - March 17th, 2019
- Neuropathy & Pain Centers of Texas - Stem Cells & Neuropathy - February 6th, 2019
- Stem Cell Doctor Dallas Dr. Darcy Brunk | Dallas, Plano ... - January 25th, 2019
- Four Types of Stem Cells - Texas Right to Life - December 15th, 2018
- Texas | The Stem Cellar - December 5th, 2018
- Dallas, Texas, Stem Cells Treatment, Legal, Ft. Worth ... - November 16th, 2018
- HB810 | Right to Try Law | Texas Stem Cell Law | StemGenex - October 13th, 2018
- Shooting Up Stem Cells With Ben Greenfield The Down The ... - September 16th, 2018