Navigation Links
Why don't all moles progress to melanoma?

Everyone has moles. Most of the time, they are nothing but a cosmetic nuisance. But sometimes pigment-producing cells in moles called melanocytes start dividing abnormally to form a deadly form of skin cancer called melanoma. About one in 65 Americans born this year will be diagnosed with melanoma at some point during their lifetime.

Scientists know that 30 percent of all melanomas begin in a mole. They know that 90 percent of moles contain cancer-causing mutations. What scientists didn't know is how melanocytes stop these mutations from triggering the development of cancer.

Maria S. Soengas, Ph.D., and other scientists in the Multidisciplinary Melanoma Clinic at the University of Michigan Comprehensive Cancer Center, have found the answer to this important question in an unexpected place ?a structure inside cells called the endoplasmic reticulum, or ER.

"Our results support the direct role of the endoplasmic reticulum as an important gatekeeper of tumor control," says Soengas, who is an assistant professor of dermatology in the U-M Medical School. "Until now, no one knew there was a connection between ER stress and the very early stages of tumor initiation."

Results of the U-M study ?involving melanocytes from normal human skin and biopsies of non-malignant human moles ?are being published in the October issue of Nature Cell Biology.

The endoplasmic reticulum is the cell's protein production factory. The process begins when chains of amino acids are deposited in the ER membrane in response to coded instructions from genes. Chaperone proteins fold these amino acids into specific shapes. When too many of them build up in the membrane, or when something goes wrong with the folding process, the system gets bogged down. This can stress or even kill the cell.

To prevent this, the ER sends out distress signals to activate what scientists call the unfolded protein response (UPR). This slows the protein production proc ess and gets rid of excess incoming amino acids, giving the ER a chance to catch up. If that doesn't work, the UPR causes the cell to destroy itself in a process called apoptosis.

"Traditionally, the ER's role was considered to be limited to protein folding or protein modification," Soengas says. "But scientists like Randal Kaufman, a U-M professor of biological chemistry and co-author on our paper, have found that the ER can sense changes in glucose, nutrients, oxygen levels and other aspects of cellular physiology associated with diseases like diabetes and Alzheimer's disease."

"In our study, we found that the ER senses the activity of certain oncogenes in the melanocyte and triggers a response that prevents the malignant transformation of these cells," Soengas adds.

According to Soengas, the tumor suppressive mechanism induced by the ER in melanocytes with these cancer-causing mutations is premature senescence ?a form of "suspended animation" that stops the cell cycle and keeps cells from dividing, but doesn't kill them.

"The cells are held in check ?they don't die, but they don't proliferate either," Soengas explains. "In the case of moles, melanocytes can stay this way for 20 to 40 years or even your whole life. For most of us, just holding cells in an arrested state is sufficient to prevent the development of cancer. That's why so many people have moles, but few have melanoma."

In the study, U-M scientists found that the tumor suppressive response in melanocytes varied depending on the type of oncogene being expressed in the cell.

"We found that some oncogenes activated the endoplasmic reticulum, while other oncogenes didn't," Soengas says.

In a previous study, Soengas and colleagues found that certain oncogenes use a different senescence mechanism, which doesn't activate the ER, to block the transformation of melanocytes. Both these mechanisms work in addition to or independent from other well- known tumor suppressor mechanisms involving apoptosis.

Soengas says the results of the study will be important in helping scientists understand all the different mechanisms melanocytes use to protect themselves against oncogenes. But she cautions that there are no immediate clinical applications for the study and additional research will be required.

In future research, Soengas will attempt to determine exactly how oncogenes trigger the unfolded protein response in malignant and non-malignant skin cells. "By comparing what happens in normal melanoctyes with what happens in melanoma, we may be able to come up with events that are specific for tumor cells, which could be used for future drug development," she says.
'"/>

Source:University of Michigan Health System


Related biology news :

1. Penguins waddle but they dont fall down, UH researchers say
2. Nearly half of people who need cholesterol treatment dont get it
3. Study: Paramedics save more lives when they dont follow the rules
4. Even fish dont swim well when theyre young!
5. One-third of adults with diabetes still dont know they have it
6. Survival of the selfless - scientists find cheats dont always prosper
7. Why mice dont get cancer of the retina
8. New cigarette designs dont offer lower predicted cancer risks
9. Some caterpillers just dont want to grow up
10. Mosquito repellents that emit high-pitched sounds dont prevent bites
11. When your brain talks, your muscles dont always listen

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/22/2016)... American College of Medical Genetics and Genomics was once again ... of the fastest-growing trade shows during the Fastest 50 Awards ... Las Vegas . Winners are ... of the following categories: net square feet of paid exhibit ... 2015 ACMG Annual Meeting was ranked 23 out of 50 ...
(Date:6/21/2016)... Columbia , June 21, 2016 ... to the new role of principal product architect ... named the director of customer development. Both will ... chief technical officer. The moves reflect NuData,s strategic ... in response to high customer demand and customer ...
(Date:6/15/2016)... June 15, 2016 Transparency ... titled "Gesture Recognition Market by Application Market - Global Industry Analysis ... 2024". According to the report, the  global gesture recognition ... 2015 and is estimated to grow at a ... by 2024.  Increasing application of gesture ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... Houston Methodist Willowbrook Hospital has signed ... to serve as their official health care provider. ... will provide sponsorship support, athletic training services, and ... volunteers, athletes and families. "We are ... and to bring Houston Methodist quality services and ...
(Date:6/23/2016)... FRANCISCO , June 23, 2016   EpiBiome ... has secured $1 million in debt financing from Silicon ... ramp up automation and to advance its drug development ... its new facility. "SVB has been an ... beyond the services a traditional bank would provide," said ...
(Date:6/23/2016)... , June 23, 2016 Apellis ... Phase 1 clinical trials of its complement C3 ... single and multiple ascending dose studies designed to ... (PD) of subcutaneous injection in healthy adult volunteers. ... (SC) either as a single dose (ranging from ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... the Pennsylvania Convention Center and will showcase its product’s latest features from June ... be presenting a scientific poster on Disrupting Clinical Trials in The Cloud during ...
Breaking Biology Technology: