Researchers discover mechanism of cell type-specific signaling in tumor development

Apr 07, 2009

Mayo Clinic researchers have discovered the mechanisms behind two key checkpoints in cell growth and development — factors that may ultimately allow investigators to benchmark progression of tumor cells or stop them from further development. The findings appear in the current online issue of Developmental Cell.

The team led by Edward Leof, Ph.D., Mayo Clinic biochemist, demonstrated that p21-activated kinase 2 (PAK2), a key target for cancer growth and fibrotic tissue development, is activated in one type of tissue but not another. PAK2 is a downstream component of transforming growth factor beta (TGF-β) signaling in mesenchymal cells — those that make up connective tissues in the body, as well as blood and lymphatic vessels. However, TGF-β is unable to activate PAK2 in — those that make up external and internal linings, such as skin and the internal lining of many vessels.

"We decided to look at the factors that prevented PAK2 activation in epithelial cells," says Dr. Leof. "We found that a protein called Erbin, in cooperation with the NF2 suppressor Merlin, controls the outcome."

Erbin, the researchers found, controls the tumor suppressor gene Merlin. When Merlin is absent or mutated, the result is schwannoma, a form of tumor involving Schwann cells which make up the myelin sheath that covers nerves. Merlin has also been shown to play a part in causing melanoma, mesothelioma and possibly colorectal cancers.

The researchers showed that in epithelial cells, which have high levels of Erbin, the formation of an Erbin/Merlin complex prevents PAK2 activity following growth factor stimulation. In the absence of Erbin (or Merlin), however, TGF-β stimulates PAK2 activity in some epithelia, overcoming a critical checkpoint in tumor progression.

The findings are important, says Dr. Leof, because they delineate a process by which tumors might be formed and allow future researchers to pinpoint steps where interventions could not just gauge disease progression, but halt tumor growth. There is even the prospect of intervening before a tumor begins to form.

Source: Mayo Clinic (news : web)

Explore further: Scientists find way to target cells resistant to chemo

add to favorites email to friend print save as pdf

Related Stories

Balancing act protects vulnerable cells from cancer

Oct 23, 2007

When a cell loses some of its weapons to fight cancer, it can still look healthy and act normally — if not forever, at least for a while. In research published in the October 15 issue of Cancer Cell, Rockefeller Univer ...

'Innocent bystanders' can be the cause of tumor development

Mar 03, 2008

Tumor growth has commonly been viewed as a result of mutations in a given cell that will therefore proliferate uncontrollably. However, a study conducted at the University of Helsinki, Finland, has demonstrated that in certain ...

Recommended for you

US OKs first-ever DNA alternative to Pap smear (Update 2)

13 hours ago

U.S. government health regulators have cleared a genetic test from Roche as a first-choice screening option for cervical cancer. It was a role previously reserved for the Pap smear, the decades-old mainstay of women's health.

New breast cancer imaging method promising

18 hours ago

The new PAMmography method for imaging breast cancer developed by the University of Twente's MIRA research institute and the Medisch Spectrum Twente hospital appears to be a promising new method that could ...

Palliation is rarely a topic in studies on advanced cancer

19 hours ago

End-of-life aspects, the corresponding terminology, and the relevance of palliation in advanced cancer are often not considered in publications on randomized controlled trials (RCTs). This is the result of an analysis by ...

User comments : 0

More news stories

Google+ boss leaving the company

The executive credited with bringing the Google+ social network to life is leaving the Internet colossus after playing a key role there for nearly eight years.