Breaking News
November 19, 2018 - Biologists uncover novel genetic control of lipid maintenance and its potential connection to lifespan
November 19, 2018 - Warmer winters may set scene for higher rates of violent crimes
November 19, 2018 - Acacia Pharma Resubmits Barhemsys New Drug Application
November 19, 2018 - PDL1 (Immunotherapy) Tests: MedlinePlus Lab Test Information
November 19, 2018 - Transforming pregnancy research with a smartphone app
November 19, 2018 - Stanford Medicine magazine explores how digital technology is changing health care
November 19, 2018 - New report calls for greater awareness and emphasis on scale and impact of atrial fibrillation
November 19, 2018 - In throes of turkey salmonella outbreak, don’t invite illness to your table
November 19, 2018 - UK health policies should be redesigned to become more accessible for men
November 19, 2018 - Short Interpregnancy Intervals Tied to Adverse Outcome Risk
November 19, 2018 - New mothers’ breastfeeding pain can affect infant health
November 19, 2018 - Stanford Medicine magazine reports on ways digital technology is transforming health care | News Center
November 19, 2018 - Human drugs alter cricket personality
November 19, 2018 - Insilico Medicine to introduce ‘Cure a disease in a year’ program at Biodata World Congress 2018
November 19, 2018 - Experts debate over whether gut or brain is more important in regulating appetite
November 19, 2018 - Playing on fear and fun, hospitals follow pharma in direct-to-consumer advertising
November 19, 2018 - 2PG Company receives grant to develop sensitive, low-cost molecular diagnostic tests for tuberculosis
November 19, 2018 - Low-Carb Diets May Work By Boosting Calorie Burn
November 19, 2018 - Key molecule responsible for learning and memory discovered
November 19, 2018 - New blood test developed for early diagnosis of ovarian cancer
November 19, 2018 - Researchers identify molecule to fight myotubular myopathy
November 19, 2018 - New solution to stop spread of brain cancer
November 19, 2018 - Immune cells trigger OCD-like behaviour in multiple sclerosis, study finds
November 19, 2018 - Scientists equip new virus that kills carcinoma cells with protein
November 19, 2018 - Novel approach could provide painless, efficient alternative for treating eye diseases
November 19, 2018 - Protein in cell membranes of sperm plays key role in finding their way to eggs
November 19, 2018 - Parents who decline flu vaccination for their child may be exposed to limited information
November 19, 2018 - Mirati Presents Data From Ongoing Phase 2 Clinical Trial Of Mocetinostat In Combination With Durvalumab At The SITC 33rd Annual Meeting
November 19, 2018 - FDA warns of common diabetes meds’ link to dangerous genital infection
November 19, 2018 - New methods for preserving shoulder function, quality of life in breast cancer patients
November 19, 2018 - Surprising discovery about BH4 may rekindle interest in once-promising pathway
November 19, 2018 - Nabriva Therapeutics Completes Submission of New Drug Application to U.S. Food and Drug Administration for Intravenous Contepo to Treat Complicated Urinary Tract Infections
November 19, 2018 - Beating breast cancer only to die of opioid use – a sad Appalachian story
November 19, 2018 - Workplace bullying or violence linked to higher risk of cardiovascular problems
November 19, 2018 - Changes in Risk Indicators of MetS Severity Tied to T2DM Risk
November 19, 2018 - ‘Game-changing’ skin sensor could improve life for a million hydrocephalus patients
November 19, 2018 - Alcohol ads on social media sites with pro-drinking comments increase desire to drink
November 19, 2018 - Neural networks could replace marker genes in RNA sequencing
November 19, 2018 - Obese adolescents feel less food enjoyment than those with normal weight, study reveals
November 18, 2018 - Goodbye ‘Gluten-Free’? Celiac Disease Vaccine May Make It Possible
November 18, 2018 - Skin ages when the main cells in the dermis lose their identity and function
November 18, 2018 - Rainforest vine compound makes pancreatic cancer cells susceptible to nutrient starvation
November 18, 2018 - A new mechanism in the control of inflammation
November 18, 2018 - Age-related decline in abstract reasoning ability predicts depressive symptoms over time
November 18, 2018 - Scientists succeed in increasing stability, biocompatibility of light-transducing nanoparticles
November 18, 2018 - Sugar, a ‘sweet’ tool to understand brain injuries
November 18, 2018 - Pharmacist-Led Effort Cuts Inappropriate Rx in Older Adults
November 18, 2018 - Novel discovery could lead to new cancer, autoimmune disease therapy
November 18, 2018 - AHA and ADA launch new initiative to help people with type 2 diabetes reduce heart disease risk
November 18, 2018 - Balanced production of pro and anti-inflammatory cytokines at two years of age protects against malaria
November 18, 2018 - New pharmacological agent shows promise for prevention of heart rhythm disorders
November 18, 2018 - All That Social Media May Boost Loneliness, Not Banish It
November 18, 2018 - Scientists shine new light on link between obesity and cancer
November 18, 2018 - Risk factors for cardiovascular disease closely track with changes in diet patterns
November 18, 2018 - Biogen Scoops Sixth Prix Galien Award with UK Win for Life-Changing Rare Disease Medicine
November 18, 2018 - Detectable HIV-1 in treated human liver cells found to be inert
November 18, 2018 - Using light to control crucial step in embryonic development
November 18, 2018 - Unusual case of father-to-son HIV transmission reported
November 18, 2018 - FDA Approves Aemcolo (rifamycin) to Treat Travelers’ Diarrhea
November 18, 2018 - Poverty blamed on widening north-south gap in young adult deaths in England
November 18, 2018 - Progress in meningitis lags far behind other vaccine-preventable diseases, analysis shows
November 18, 2018 - Consensus Statement Issued on Management of Foot, Ankle Gout
November 18, 2018 - Fine particle air pollution is a public health emergency hiding in plain sight
November 18, 2018 - In-hospital mortality higher among patients with drug-resistant infections
November 17, 2018 - Research shines new, explanatory light on link between obesity and cancer
November 17, 2018 - FIND explores new diagnostic assays for confirmatory HCV diagnosis in community settings
November 17, 2018 - Tracking Preemies’ Head Size May Yield IQ Clues
November 17, 2018 - Scientists call for unified standards in 3-D genome and epigenetic data
November 17, 2018 - Lab Innovations 2018 has beaten all records by attracting 3,113 attendees
November 17, 2018 - New strategy to hinder emergence of antimicrobial-resistant pathogens
November 17, 2018 - Sexuality education before age 18 may reduce risk of sexual assault in college
November 17, 2018 - Reducing cellular proliferation could help deplete HIV reservoir and lead to a functional cure
November 17, 2018 - New model of FSHD could be useful to study effectiveness of experimental therapeutics
November 17, 2018 - FDA approves antibacterial drug to treat travelers’ diarrhea
November 17, 2018 - Lab Innovations 2018 confirmed as a major hit with visitors, exhibitors and speakers
November 17, 2018 - Largest parasitic worm genetic study hatches novel treatment possibilities
November 17, 2018 - UCLA biologists uncover how head injuries can lead to serious brain disorders
November 17, 2018 - Static and dynamic physical activities offer varying protection against heart disease
November 17, 2018 - Obesity significantly increases risk of Type 2 diabetes and coronary artery disease
November 17, 2018 - New method to analyze cell membrane complexes could revolutionize the way we study diseases
Study unravels how cancer stem cells use normal genes in abnormal ways

Study unravels how cancer stem cells use normal genes in abnormal ways

image_pdfDownload PDFimage_print

CDK1 is a “normal” protein – its presence drives cells through the cycle of replication. And MHC Class I molecules are “normal” as well – they present bits of proteins on the surfaces of cells for examination by the immune system. But a University of Colorado Cancer Center study published in the journal Cancer Research shows that a population of cancer cells marked by MHC Class I molecules and high CDK1 is anything but normal. In fact, these MHC Class I-high, CDK1 high molecules may be at the heart of conditions including melanoma, pancreatic and colon cancers. These cells may, in fact, be the long-sought cancer stem cells that often resist treatments like chemotherapy to reseed these cancers once treatment ends.

From the outset, the goal of this study was different than most. Often, cancer researchers will grow tumors and then ask what kinds of drugs or genetic changes make tumors grow or shrink. However, the current study wondered not what makes tumors change size, but what factors in these cells initiate tumor growth in the first place. To answer this question, the study used patient samples, mouse models and publicly available genetic data to search for the genetic/genomic commonalities in cells capable of initiating melanoma, pancreatic and colon cancers.

The findings start with a molecule called MHC Class I, a common molecule that coats the outside of human cells and functions a bit like a hand waving a flag. When MHC Class I molecules wave “flags” (actually bits of proteins), that are not from host tissue, the immune system recognizes the cell as foreign and attacks it. For this reason, most cancer cells downregulate MHC as a way of evading the immune system.

But the current study shows that the population of cancer cells able to initiate the formation of new tumors does not downregulate MHC Class I molecules. In fact, if anything this special population of cancer cells upregulates MHC Class I molecules.

“Probably, these cells have another way to evade the immune system,” says Mayumi Fujita, MD, PhD, investigator at CU Cancer Center and professor in the CU School of Medicine Departments of Dermatology and Immunology/Microbiology.

Oddly, this population of cancer cells that retains MHC Class I molecules also retains another feature of healthy cells, namely the presence of a protein called CDK1. CDK1 is a master regulator of the cell cycle – with CDK1, cells progress through the cycle of replication; without CDK1, they do not. In this case, the more CDK1, the more able melanoma cells were to initiate new tumors.

“Our next question was why,” Fujita says. “Why would CDK1 control not just the cell cycle, but also stem-ness?”

Finally, the answer includes something that is not “normal.” Sox2 is a transcription factor that helps embryonic and neural stem cells keep their stem-ness. It is also a known marker of cancer stem cells, implicated in the development of more than 25 forms of the disease. Despite its identification as a driver of cancer, Sox2 remains a difficult target.

“It’s very difficult to control a transcription factor like Sox2. We can show Sox2 is very important for tumorigenesis, but it’s difficult to have a Sox2 inhibitor,” Fujita says.

However, the current study found that CDK1 directly interacted with Sox2 to keep these cancer cells “stemmy.” And here is the important part: “If CDK1 controls Sox2 function through this interaction, probably we can someday inhibit it, maybe through some way of targeting CDK1 or perhaps some way to interfere with the interaction of CDK1 with Sox2,” Fujita says.

Importantly, this signature of MHC Class 1, CDK1 and Sox2 was common across melanoma, colon and pancreatic cancers, implying that cancer stem cells across cancer types may share common features.

“We can’t say that all tumor types have this signature, but it’s prevalent. We think probably this phenotype is very common in melanoma, pancreatic and colon cancer,” Fujita says.

Moving forward, the Fujita group hopes to further define the mechanism of Sox2 regulation via CDK1 in hopes of finding essential links that might be targets for new drugs aimed, eventually, at stopping the action of Sox2.

Source:

Cancer stem cells use “normal” genes in abnormal ways

Tagged with:

About author

Related Articles