Featured Research

from universities, journals, and other organizations

Renal Cancer: Protein Triggers A Snowball Effect

November 2, 2009
ETH Zurich
If a certain protein is missing in kidney cells, fatal cell division errors arise, which can finally lead to genetically unstable cells and to renal cancer. Researchers have tracked down the phenomenon.

With different colouring methods the researchers showed that the protein VHL binds to the spindle apparatus during different stages of the cell division. The chromosomes (blue) are thus distributed on the daughter cells.

If a certain protein is missing in kidney cells, fatal cell division errors arise, which can finally lead to genetically unstable cells and to renal cancer. ETH researchers tracked down the phenomenon.

Related Articles

Body cells divide incessantly. This is actually a "standard procedure", which in most cases proceeds without error. Particularly important during cell division, known as mitosis, is the correct distribution of the chromosomes to the new daughter cells. This requires that a spindle of microtubules is formed in the cell during the division, with the aid of which the chromosomes are pulled to the opposite poles.

Here, the fidelity-monitoring checkpoint system plays an important role. It supervises whether all chromosomes are correctly bound to the spindle microtubules. This checkpoint is activated, if errors arise during cell division, which would lead to an unequal distribution of the chromosomes on the daughter cells. The spindle checkpoint can halt cell division for as long as necessary, until the chromosomes are correctly attached to the spindle microtubulues.

Fatal consequences upon loss of a protein

With this mechanism the cell prevents the formation and accumulation of cells with abnormal sets of chromosomes. Now, however, in a publication in "Nature Cell Biology" two ETH researchers, the cell biologist Claudio Thoma from the Wilhelm Krek working group and the biochemist Alberto Toso from the Patrick Meraldi group, have identified a mechanism, which triggers an unwanted and fatal snowball effect, which can lead to kidney cells with deviating chromosome numbers and contribute to kidney cancer development.

Central to this mechanism is the von Hippel Lindau tumor suppressor protein (pVHL). During cell division this molecule is deposited on the spindle apparatus. If pVHL is missing, the cells divide incorrectly. The spindle cannot align itself correctly and changes its position like a defective compass needle. The spindle checkpoint is also weakened. With a loss of pVHL cell division continues, chromosomes are lost; cells with incomplete or overstaffed chromosome sets develop. Aneuploid cells emerge, which contain the wrong number of chromosomes, are genetically unstable and are thus dangerous.

Metabolic conversion instead of cell death

A further unwanted effect of the pVHL deficiency: aneuploid cells do not die. If the molecule precipitates, these cells even switch over to a very efficient mode of energy production. They divide more vigorously, grow exuberantly and form cysts, which are considered as precoursor states of tumours. "80 per cent of the tumours in human cells have an abnormal number of chromosomes", states Wilhelm Krek, Professor of Cell Biology.

The loss of pVHL is in part hereditary due to mutations of the gene. There are two copies of the VHL gene. If one copy is already defective at birth, it only needs a mutation or a blockade of the second copy, for cells to no longer produce pVHL.

Medicine against degenerate cells?

Krek is convinced that the new findings on the role of pVHL have a therapeutic use. The greatest chance of success is probably in the fight against aneuploid cells. According to the ETH professor they now need to find a drug which kills them preferentially. Kidney cancer is considered as an aggressive type of cancer, since it often forms offshoots, so-called metastasis. 60 per cent of all patients, who get it, die 5 to 8 years after the treatment, because of the development of metastases, which can no longer be combatted.

Why pVHL plays such an important role only in the kidney cells, with the emergence of degenerate cells, is still unclear, because both the spindle apparatus and the protein is present in all body cells during cell division.

Cell procedures observed in real time

The work developed in a co-operation between cell biologists and biochemists, where the original authors of the paper, which was published in Nature Cell Biology, by chance exchanged views concerning their own special fields and discovered the close link between pVHL and cell division. Thanks to "Single Cell Life Imaging", a special optical microscope technology, the researchers could observe and follow living cells individually. The Light Microscopy Centre of the ETH Zurich, which offers the technology, is at the forefront of this technology.

Story Source:

The above story is based on materials provided by ETH Zurich. Note: Materials may be edited for content and length.

Journal Reference:

  1. Thoma et al. VHL loss causes spindle misorientation and chromosome instability. Nature Cell Biology, 2009; 11 (8): 994 DOI: 10.1038/ncb1912

Cite This Page:

ETH Zurich. "Renal Cancer: Protein Triggers A Snowball Effect." ScienceDaily. ScienceDaily, 2 November 2009. <www.sciencedaily.com/releases/2009/09/090911212654.htm>.
ETH Zurich. (2009, November 2). Renal Cancer: Protein Triggers A Snowball Effect. ScienceDaily. Retrieved April 2, 2015 from www.sciencedaily.com/releases/2009/09/090911212654.htm
ETH Zurich. "Renal Cancer: Protein Triggers A Snowball Effect." ScienceDaily. www.sciencedaily.com/releases/2009/09/090911212654.htm (accessed April 2, 2015).

Share This

More From ScienceDaily

More Health & Medicine News

Thursday, April 2, 2015

Featured Research

from universities, journals, and other organizations

Featured Videos

from AP, Reuters, AFP, and other news services

Wound-Healing Laser Soon to Be a Reality Israeli Scientist

Wound-Healing Laser Soon to Be a Reality Israeli Scientist

Reuters - Innovations Video Online (Apr. 1, 2015) Israeli scientists says laser bonding of tissue allows much faster healing and less scarring. Amy Pollock has more. Video provided by Reuters
Powered by NewsLook.com
Liberia Sees Resurgence of Drug Trafficking as Ebola Wanes

Liberia Sees Resurgence of Drug Trafficking as Ebola Wanes

AFP (Apr. 1, 2015) The governments of Liberia and Sierra Leone have been busy fighting the menace created by the deadly Ebola virus, but illicit drug lords have taken advantage of the situation to advance the drug trade. Duration: 01:12 Video provided by AFP
Powered by NewsLook.com
Stigma Stalks India's Leprosy Sufferers as Disease Returns

Stigma Stalks India's Leprosy Sufferers as Disease Returns

AFP (Apr. 1, 2015) The Indian government declared victory over leprosy in 2005, but the disease is making a comeback in some parts of the country, with more than a hundred thousand lepers still living in colonies, shunned from society. Duration: 02:41 Video provided by AFP
Powered by NewsLook.com
7-Year-Old Girl Gets 3-D Printed 'robohand'

7-Year-Old Girl Gets 3-D Printed 'robohand'

AP (Mar. 31, 2015) Although she never had much interest in prosthetic limbs before, Faith Lennox couldn&apos;t wait to slip on her new robohand. The 7-year-old, who lost part of her left arm when she was a baby, grabbed it as soon as it came off a 3-D printer. (March 31) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.


Breaking News:

Strange & Offbeat Stories

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News


Free Subscriptions

Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile

Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?

Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins