Breaking News
April 25, 2019 - Association Insurance Pushes On Despite Court Ruling
April 25, 2019 - Traditional and e-cigarette users may be more receptive to smoking cessation interventions
April 25, 2019 - Delving into tumor’s cellular lineage may offer clues for customized therapies
April 25, 2019 - Two studies uncover brain mechanisms underlying decision making process
April 25, 2019 - Cardiometabolic Risk Better ID’d in Children Reclassified to Higher BP
April 25, 2019 - How the obesity epidemic is taking a toll on our bones and joints
April 25, 2019 - E-cigarettes contaminated with dangerous microbial toxins
April 25, 2019 - Researchers document specific characteristics of storefront tobacco advertisements
April 25, 2019 - Oncotype DX-guided treatment could reduce cost for breast cancer care, study suggests
April 25, 2019 - New review highlights how lifestyle affects our genes
April 25, 2019 - Study provides evidence that blood tests can detect Alzheimer’s risk
April 25, 2019 - Computer program mimics natural speech using brain signals from epilepsy patients
April 25, 2019 - Physicians turning to antibiotic alternatives for long-term acne treatment
April 25, 2019 - Preschool Is Prime Time to Teach Healthy Lifestyle Habits
April 25, 2019 - Study finds insidious and persistent discrimination among physician mothers
April 25, 2019 - Newly identified skin-gut communication helps illuminate link between food allergy and eczema
April 25, 2019 - Thiazide use linked with reduced risk of low energy fractures in people with Alzheimer’s
April 25, 2019 - Some women are biologically more resilient than others to PTSD
April 25, 2019 - The Current issue of “The view from here” is concerned with Partnerships and Alliances
April 25, 2019 - Imaging method reveals long-lived patterns in cells of the eye
April 25, 2019 - Podcast: KHN’s ‘What The Health?’ The Abortion Wars Rage On
April 25, 2019 - Prolonged exposure therapy is more effective in treating veterans with PTSD, alcohol use disorder
April 24, 2019 - Our artificial cornea breakthrough could lead to self-assembling organs
April 24, 2019 - A Stanford black, female, gay surgery resident speaks out
April 24, 2019 - Donna Lynne on Extreme Sports, Lessons From the '60s, and Taking CUIMC to the Next Level
April 24, 2019 - Pain Clinics’ Doctors Needlessly Tested Hundreds Of Urine Samples, Court Records Show
April 24, 2019 - Researchers uncover potential clue to halt destruction of nerve cells in people with ALS
April 24, 2019 - Study uncovers reasons for poor mental health in bisexual people
April 24, 2019 - Screenings, interventions, and referrals can help adolescents overcome substance abuse
April 24, 2019 - Febrile seizures following vaccination are self-resolving and not dangerous
April 24, 2019 - Flow-UV inline UV-Visible spectrometer monitors dispersion in real time
April 24, 2019 - Rates of Marijuana Use in Cancer Patients on the Rise in U.S.
April 24, 2019 - Versatile drug may protect baby from hazards of intraamniotic infections
April 24, 2019 - Financial transparency may diminish trust in doctors, new study finds
April 24, 2019 - Calling all Riders: Velocity Extends Free Registration 
April 24, 2019 - The Homeless Are Dying In Record Numbers On The Streets Of L.A.
April 24, 2019 - Researchers use brain scans to provide better understanding of unconscious bias
April 24, 2019 - Blocking BRAF ubiquitination may be an effective treatment approach in melanoma
April 24, 2019 - Simple mobility test helps predict hospital readmission in elderly heart attack patients
April 24, 2019 - Novel fluorescence imaging system helps surgeons remove small ovarian tumors
April 24, 2019 - Uncovering the Structure of HIV Integrase to Inform Drug Discovery
April 24, 2019 - Medical Marijuana Use Rising Among Cancer Patients
April 24, 2019 - Artificial intelligence approach optimizes embryo selection for IVF
April 24, 2019 - Doctor or detective? Sleuthing mysteries in medical school
April 24, 2019 - CUIMC Community Gives Blood During Spring 2019 Columbia University Blood Drive
April 24, 2019 - Americans Overwhelmingly Want Federal Protections Against Surprise Medical Bills
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Ambiguous genitalia in newborns may be more common than previously thought
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
April 24, 2019 - DNA rearrangement may predict poor outcomes in multiple myeloma
April 24, 2019 - FDA Approves Skyrizi (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis
April 24, 2019 - Combination therapy might be beneficial in schizophrenia
April 24, 2019 - Blood test can help match cancer patients to early phase clinical trials
April 24, 2019 - Women tend to underreport snoring and underestimate its loudness
April 24, 2019 - Comprehensive molecular test introduced for diagnosis of malaria caused by P. vivax parasites
April 24, 2019 - New range prediction approach increases accuracy, safety and tolerability of proton therapy
April 24, 2019 - Need for Sedation Up for Regular Cannabis Users
April 24, 2019 - Lack of access to antibiotics is a major global health challenge
Cancer stem cells use ‘normal’ genes in abnormal ways

Cancer stem cells use ‘normal’ genes in abnormal ways

image_pdfDownload PDFimage_print
Mayumi Fajita, MD, PhD and colleagues show that CDK1 interacts with Sox2 to keep cancer stem cells ‘stemmy’. Credit: University of Colorado Cancer Center

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, Ph.D., 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.


Explore further:
Blocking molecular target could make more cancers treatable with PARP inhibitors

More information:
Dinoop Ravindran Menon et al, CDK1 interacts with Sox2 and promotes tumor initiation in human melanoma, Cancer Research (2018). DOI: 10.1158/0008-5472.CAN-18-0330

Journal reference:
Cancer Research

Provided by:
CU Anschutz Medical Campus

Tagged with:

About author

Related Articles