Tag Archives: biology

Musashi proteins, stained red, appear in the cell cytoplasm, outside the nucleus. At right, the cell nucleus is stained blue.
Image Credit: Yarden Katz/MIT

Proteins drive cancer cells to change states

When RNA-binding proteins are turned on, cancer cells get locked in a proliferative state.

 By Anne Trafton


 

A new study from MIT implicates a family of RNA-binding proteins in the regulation of cancer, particularly in a subtype of breast cancer. These proteins, known as Musashi proteins, can force cells into a state associated with increased proliferation.

Biologists have previously found that this kind of transformation, which often occurs in cancer cells as well as during embryonic development, is controlled by transcription factors — proteins that turn genes on and off. However, the new MIT research reveals that RNA-binding proteins also play an important role. Human cells have about 500 different RNA-binding proteins, which influence gene expression by regulating messenger RNA, the molecule that carries DNA’s instructions to the rest of the cell.

“Recent discoveries show that there’s a lot of RNA-processing that happens in human cells and mammalian cells in general,” says Yarden Katz, a recent MIT PhD recipient and one of the lead authors of the new paper. “RNA is processed at several points within the cell, and this gives opportunities for RNA-binding proteins to regulate RNA at each point. We’re very interested in trying to understand this unexplored class of RNA-binding proteins and how they regulate cell-state transitions.”

Feifei Li of China Agricultural University is also a lead author of the paper, which appears in the journal eLife on Dec. 15. Senior authors of the paper are MIT biology professors Christopher Burge and Rudolf Jaenisch, and Zhengquan Yu of China Agricultural University.

Controlling cell states

Until this study, scientists knew very little about the functions of Musashi proteins. These RNA-binding proteins have traditionally been used to identify neural stem cells, in which they are very abundant. They have also been found in tumors, including in glioblastoma, a very aggressive form of brain cancer.

“Normally they’re marking stem and progenitor cells, but they get turned on in cancers. That was intriguing to us because it suggested they might impose a more undifferentiated state on cancer cells,” Katz says.

To study this possibility, Katz manipulated the levels of Musashi proteins in neural stem cells and measured the effects on other genes. He found that genes affected by Musashi proteins were related to the epithelial-to-mesenchymal transition (EMT), a process by which cells lose their ability to stick together and begin invading other tissues.

EMT has been shown to be important in breast cancer, prompting the team to look into Musashi proteins in cancers of non-neural tissue. They found that Musashi proteins are most highly expressed in a type of breast tumors called luminal B tumors, which are not metastatic but are aggressive and fast-growing.

When the researchers knocked down Musashi proteins in breast cancer cells grown in the lab, the cells were forced out of the epithelial state. Also, if the proteins were artificially boosted in mesenchymal cells, the cells transitioned to an epithelial state. This suggests that Musashi proteins are responsible for maintaining cancer cells in a proliferative, epithelial state.

“These proteins seem to really be regulating this cell-state transition, which we know from other studies is very important, especially in breast cancer,” Katz says.

Musashi proteins, stained red, appear in the cell cytoplasm, outside the nucleus. At right, the cell nucleus is stained blue. Image Credit: Yarden Katz/MIT
Musashi proteins, stained red, appear in the cell cytoplasm, outside the nucleus. At right, the cell nucleus is stained blue.
Image Credit: Yarden Katz , MIT

 

The researchers found that Musashi proteins repress a gene called Jagged1, which in turn regulates the Notch signaling pathway. Notch signaling promotes cell division in neurons during embryonic development and also plays a major role in cancer.

When Jagged1 is repressed, cells are locked in an epithelial state and are much less motile. The researchers found that Musashi proteins also repress Jagged1 during normal mammary-gland development, not just in cancer. When these proteins were overexpressed in normal mammary glands, cells were less able to undergo the type of healthy EMT required for mammary tissue development.

Brenton Graveley, a professor of genetics and developmental biology at the University of Connecticut, says he was surprised to see how much influence Musashi proteins can have by controlling a relatively small number of genes in a cell. “Musashi proteins have been known to be interesting for many years, but until now nobody has really figured out exactly what they’re doing, especially on a genome-wide scale,” he says.

The researchers are now trying to figure out how Musashi proteins, which are normally turned off after embryonic development, get turned back on in cancer cells. “We’ve studied what this protein does, but we know very little about how it’s regulated,” Katz says.

He says it is too early to know if the Musashi proteins might make good targets for cancer drugs, but they could make a good diagnostic marker for what state a cancer cell is in. “It’s more about understanding the cell states of cancer at this stage, and diagnosing them, rather than treating them,” he says.

The research was funded by the National Institutes of Health.

Source : MIT News Office

Professor Jim Westwood has discovered that parasitic plants and their hosts have extensive communications with each other and exchange vast amounts of information. He used dodder and tomato plants, shown in this time-lapse video, for his experiment that measured the exchange of mRNA between species. Credit: Virginia  Tech News

Plants may use language to communicate with each other, Virginia Tech researcher finds

BLACKSBURG, Va., Aug. 15, 2014 – A Virginia Tech scientist has discovered a potentially new form of plant communication, one that allows them to share an extraordinary amount of genetic information with one another.

The finding by Jim Westwood, a professor of plant pathology, physiology, and weed sciencein the College of Agriculture and Life Sciences, throws open the door to a new arena of science that explores how plants communicate with each other on a molecular level. It also gives scientists new insight into ways to fight parasitic weeds that wreak havoc on food crops in some of the poorest parts of the world.

Professor Jim Westwood has discovered that parasitic plants and their hosts have extensive communications with each other and exchange vast amounts of information. He used dodder and tomato plants, shown in this time-lapse video, for his experiment that measured the exchange of mRNA between species. Credit: Virginia  Tech News
Professor Jim Westwood has discovered that parasitic plants and their hosts have extensive communications with each other and exchange vast amounts of information. He used dodder and tomato plants, shown in this time-lapse video, for his experiment that measured the exchange of mRNA between species. Credit: Virginia Tech News

His findings were published on Aug. 15 in the journal Science.

“The discovery of this novel form of inter-organism communication shows that this is happening a lot more than any one has previously realized,” said Westwood, who is an affiliated researcher with the Fralin Life Science Institute. “Now that we have found that they are sharing all this information, the next question is, ‘What exactly are they telling each other?’.”

Parasitic Plant Time lapse – Virginia Tech

Westwood examined the relationship between a parasitic plant, dodder, and two host plants, Arabidopsis and tomatoes. In order to suck the moisture and nutrients out the host plants, dodder uses an appendage called a haustorium to penetrate the plant. Westwood previously broke new ground when he found that during this parasitic interaction, there is a transport of RNA between the two species. RNA translates information passed down from DNA, which is an organism’s blueprint.

His new work expands this scope of this exchange and examines the mRNA, or messenger RNA, which sends messages within cells telling them which actions to take, such as which proteins to code. It was thought that mRNA was very fragile and short-lived, so transferring it between species was unimaginable.

But Westwood found that during this parasitic relationship, thousands upon thousands of mRNA molecules were being exchanged between both plants, creating this open dialogue between the species that allows them to freely communicate.

Through this exchange, the parasitic plants may be dictating what the host plant should do, such as lowering its defenses so that the parasitic plant can more easily attack it. Westwood’s next project is aimed at finding out exactly what the mRNA are saying.

Using this newfound information, scientists can now examine if other organisms such a bacteria and fungi also exchange information in a similar fashion. His finding could also help solve issues of food scarcity.

“Parasitic plants such as witchweed and broomrape are serious problems for legumes and other crops that help feed some of the poorest regions in Africa and elsewhere,” said Julie Scholes, a professor at the University of Sheffield, U.K., who is familiar with Westwood’s work but was not part of this project. “In addition to shedding new light on host-parasite communication, Westwood’s findings have exciting implications for the design of novel control strategies based on disrupting the mRNA information that the parasite uses to reprogram the host.”

Westwood said that while his finding is fascinating, how this is applied will be equally as interesting.

“The beauty of this discovery is that this mRNA could be the Achilles hill for parasites,” Westwood said. “This is all really exciting because there are so many potential implications surrounding this new information.”

Nationally ranked among the top research institutions of its kind, Virginia Tech’s College of Agriculture and Life Sciences focuses on the science and business of living systems through learning, discovery, and engagement. The college’s comprehensive curriculum gives more than 3,100 students in a dozen academic departments a balanced education that ranges from food and fiber production to economics to human health. Students learn from the world’s leading agricultural scientists, who bring the latest science and technology into the classroom.

Source: Virginia Tech