How NORE1A acts as a barrier to tumor growth

March 16, 2015
Activated Ras induces cell senescence (blue) are shown in the presence (left), but not the absence (right), of NORE1A. Credit: Clark Lab

Researchers reveal how cells protect themselves from a protein that is a key driver of cancer. The study appears in The Journal of Cell Biology.

Mutations that activate a protein called Ras drive excessive cell proliferation associated with cancer, but their ability to promote is limited by the fact that they also induce cells to exit the cell cycle and become dormant, or senescent. How active Ras mutants induce senescence, and how this pathway is disrupted in cancer cells is still unclear.

Geoffrey Clark and colleagues from the University of Louisville examined the role of the tumor suppressor NORE1A, a protein that binds to active Ras. Overexpressing NORE1A induced , whereas removing the protein prevented senescence and enhanced the transformation of cells with cancer-promoting Ras mutations.

The researchers found that Ras enhanced NORE1A's association with a kinase called HIPK2, and that this interaction was required for cell senescence. NORE1A promoted HIPK2's association with p53, a that plays a major role in restricting cancer development. HIPK2 is known to modify p53 in ways that cause either apoptosis, a kind of cell suicide, or senescence. Clark and colleagues found that NORE1A enhanced the senescence pathway.

The findings delineate how NORE1A allows Ras to modulate and induce cell senescence, and the loss of NORE1A may be a critical step in the growth of tumors.

Explore further: Restoring ability to halt cell division may protect lung cells from cancer

More information: Donninger, H., et al. 2015. J. Cell Biol. DOI: 10.1083/jcb.201408087

Related Stories

Restoring ability to halt cell division may protect lung cells from cancer

March 2, 2015
Researchers led by a team at the University of Illinois at Chicago, have identified a novel role for a signaling mechanism in lung cells that permanently places them into a state of suspended animation called senescence. ...

Tipping the balance between senescence and proliferation

November 15, 2013
An arrest in cell proliferation, also referred to as cellular senescence, occurs as a natural result of aging and in response to cellular stress. Senescent cells accumulate with age and are associated with many aging phenotypes, ...

Clipping proteins that package genes may limit abnormal cell growth in tumors

November 21, 2014
Changes to the structure of the protein histone H3.3 may play a key role in silencing genes that regulate cancer cell growth, according to a study led by researchers from the Icahn School of Medicine at Mount Sinai and published ...

A protein on which two molecular pathways converge could be the key to new cancer therapies

February 4, 2015
Two molecular pathways—one that causes cancer and one that protects against it—compete to control cellular levels of one protein, according to a new study by A*STAR researchers and colleagues.The finding highlights a ...

Recommended for you

Targeted antibiotic use may help cure chronic myeloid leukaemia

September 19, 2017
The antibiotic tigecycline, when used in combination with current treatment, may hold the key to eradicating chronic myeloid leukaemia (CML) cells, according to new research.

Bone marrow protein a 'magnet' for passing prostate cancer cells

September 19, 2017
Scientists at the University of York have shown that a protein in the bone marrow acts like a 'magnetic docking station' for prostate cancer cells, helping them grow and spread outside of the prostate.

Brain cancer breakthrough could provide better treatment

September 19, 2017
A new discovery about the most common type of childhood brain cancer could transform treatment for young patients by enabling doctors to give the most effective therapies.

Researchers compose guidelines for handling CAR T cell side effects

September 19, 2017
Immune-cell based therapies opening a new frontier for cancer treatment carry unique, potentially lethal side effects that provide a new challenge for oncologists, one addressed by a team led by clinicians at The University ...

A new paradigm for treating transcription factor-driven cancers

September 18, 2017
In the current issue of Proceedings of the National Academy of Sciences, researchers from Nationwide Children's Hospital describe a new paradigm for treating transcription factor-driven cancers. The study focuses on Ewing ...

Altitude training for cancer-fighting cells

September 18, 2017
Mountain climbers and endurance athletes are not the only ones to benefit from altitude training - that is, learning to perform well under low-oxygen conditions. It turns out that cancer-fighting cells of the immune system ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.