Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

'Mahjong' gene is key player when cancer, normal cells compete

14.07.2010
Journal PLoS Biology reports novel findings by Florida State and London researchers

A landmark study by Florida State University biologists, in collaboration with scientists in Britain, is the first to identify a life-or-death "cell competition" process in mammalian tissue that suppresses cancer by causing cancerous cells to kill themselves.

Central to their discovery was the researchers' identification of "Mahjong" –– a gene that can determine the winners of the competition through its close relationship with another powerful protein player. Lead author Yoichiro Tamori and Associate Professor Wu-Min Deng of Florida State and Yasuyuki Fujita of University College London named the newfound gene after the Chinese game of skill and luck.

The findings shed light on the critical interactions between cancerous cells and surrounding tissue, and confirm that those interactions occur not only in fruit fly models but also in mammalian cell cultures.

Tamori and team found that Mahjong binds to and interacts with the tumor suppressor gene "Lethal giant larvae" (Lgl). That bond allows Mahjong to influence the outcome of cell competition, because it is mutations in Lgl –– or in genes interacting with it –– that transform a normal cell into a malignant one, triggering the lethal showdown between neighboring healthy cells and cancerous ones.

"A better understanding of the ways that inherited or acquired mutations in key proteins lead to cell competition should help foster new therapies that increase the odds of victory for normal cells," said Tamori, a postdoctoral fellow in Florida State's Department of Biological Science.

PLoS Biology will publish the findings, which the researchers describe in their paper "Involvement of Lgl and Mahjong/VprBP in Cell Competition." The article can be accessed online after 5 p.m. EDT July 13 at www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000422.

The study began with a focus on Lgl, a gene that normally prevents the development of tumors by tightly controlling cell asymmetry and proliferation. To more fully understand its role in cell competition, the Florida State and University College London biologists looked at Lgl in both fruit flies and mammals. They knew that earlier studies of Lgl's structural qualities had concluded that it worked in tandem with other proteins. To try to identify its possible partners, the researchers used a technique that worked to trap both Lgl and any proteins bound to it.

They learned that Lgl had just one binding partner –– soon to be known as Mahjong.

"In addition to identifying Mahjong and its relationship with Lgl," said Deng, "we confirmed that both genes function in the same pathway ¬¬in both fruit flies and mammals to regulate cellular competitiveness."

To determine if a mutation would induce cell competition in fruit flies, the Florida State biologists modified fly larvae by deleting the Mahjong gene from subsets of the wing-tissue cells.

Then, using a fluorescent probe that can identify cells undergoing apoptosis (a form of programmed suicide), they saw that cell death was occurring in the Mahjong mutant cells that were adjacent to normal cells, but not in those surrounded by fellow Mahjong mutants.

"In competition with their normal neighbors," said Tamori, "cells without Mahjong were the losers."

After Tamori and Deng confirmed the role of Mahjong in fruit fly cell competition, their collaborators at University College London sought to induce competition in mammalian cells.

To replicate as closely as possible the occurrence of mutations caused by environmental factors, Fujita and his team engineered kidney cells whose copies of the Mahjong gene could be shut down by the antibiotic tetracycline. Before adding tetracycline, they mixed the engineered cells with normal ones and allowed them to grow and form tissue.

"When tetracycline was added to the tissue, the cells in which Mahjong had been shut down began to die, just as they had in the fruit fly," Tamori said.

"In the kidney cells, as in flies," he said, "apoptosis was only observed in Mahjong mutants when they were surrounded by normal cells. We now had a clear demonstration of cell competition in mammalian tissue, triggered by mutations in a key protein."

Next, the team sought to prevent apoptosis in cells that lacked Lgl or Mahjong by copying the remaining protein partner in larger-than-normal numbers.

"We learned that overexpressing Mahjong in Lgl-deficient cells, which typically self destruct, did in fact prevent apoptosis," Deng said. "But, in contrast, we found that overexpressing Lgl in Mahjong-deficient cells did not prevent cell suicide."

Funding for the study came from a five-year grant to Deng from the National Institutes of Health (NIH). A developmental and cell biologist at Florida State since 2004, Deng is recognized for research in the model organism Drosophila melanogaster (fruit fly) that has enhanced understanding of gene regulation and signaling pathways linked to cancer and other diseases.

Deng's NIH grant supported another recent study that also has advanced cancer research. In collaboration with scientists from the Johns Hopkins University School of Medicine, Deng and Florida State colleagues studying the "Hippo" tumor suppressor pathway identified an influential new gene there, which they named "Kibra." Their findings were published Feb. 16, 2010, in the journal Developmental Cell and discussed in the April 2010 issue of Nature Reviews Cancer.

Tamori and Deng of Florida State University and Fujita of University College London co-authored the PLoS Biology paper "Involvement of Lgl and Mahjong/VprBP in Cell Competition" with support from a team comprised of a postdoctoral fellow, graduate and undergraduate students, and a technician. From FSU, the team members were Ai-Guo Tian, Yi-Chun Huang, Nicholas Harrison and John Poulton. From UCL, they were Carl Uli Bialucha, Mihoko Kajita, Mark Norman, Kenzo Ivanovitch, Lena Disch and Tao Liu.

Yoichiro Tamori | EurekAlert!
Further information:
http://www.bio.fsu.edu

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>