Researchers shed light on how tumor cells form

Jun 21, 2006
Researchers shed light on how tumor cells form
Chromosomes (blue) are shown being pulled apart by microtubules (red). The green represents the cement-like substance that establishes the connection between microtubules and chromosomes. MIT researchers recently pinpointed two proteins that are key to normal cell division. Image courtesy / Viji Draviam

MIT cancer researchers have discovered a process that may explain how some tumor cells form, a discovery that could one day lead to new therapies that prevent defective cells from growing and spreading.

The work was reported June 8 in the advance online issue of The EMBO Journal, a publication of the European Molecular Biology Organization (EMBO).

Tumor cells that grow aggressively often have an irregular number of chromosomes, the structures in cells that carry genetic information. The normal number of chromosomes in a human cell is 46, or 23 pairs. Aggressive tumor cells often have fewer or more than 23 pairs of chromosomes, a condition called aneuploidy.

To date it has not been clear how tumor cells become aneuploid.

"Checkpoint proteins" within cells work to prevent cells from dividing with an abnormal number of chromosomes, but scientists have been puzzled by evidence that aneuploidy can result even when these proteins appear to be normal.

What MIT researchers have discovered is a reason these checkpoint proteins may be unable to sense the defective cells, which tend to have very subtle errors in them. (These subtle errors are believed to be the cause of aneuploidy and the rapid growth of tumors.)

Before cells divide, individual chromosomes in each pair of chromosomes must attach to a set of tiny structures called microtubules. If they attach correctly, the checkpoint proteins give them the go-ahead to divide. If they don't, the checkpoint proteins are supposed to stop them from dividing.

"The checkpoint proteins are like referees in a tug-of-war contest," said Viji Draviam, a research scientist in MIT's Department of Biology and lead author of the paper. "They make sure that all chromosomes are lined up in the right places before the cell is allowed to divide."

Scientists have known about the function of checkpoint proteins for at least 20 years, and they have suspected that mutations in checkpoint proteins cause the irregular number of chromosomes in the aneuploid cells. But they have been perplexed by the infrequent occurrence of mutations in aneuploid tumors.

"It's puzzling that the suspected culprits - the aneuploidy-inducing checkpoint mutations - are rarely found at the scene of the crime, in the aneuploid tumors," Draviam said.

That lingering question prompted Draviam and her colleagues to study how two other key molecules - a known tumor suppressor protein called APC and its partner protein EB1 - work together to assure that cells divide normally.

They discovered that if they removed either protein from a cell or if they interrupted the way the proteins work together, the cell would become aneuploid. In other words, the checkpoint proteins need to sense that the APC and EB1 proteins both are present for normal cell division to take place.

"This is important because it is the first demonstration that interrupting the normal function of these proteins will cause the cell to become aneuploid," Draviam said. "Our research sheds light on what could go wrong to cause an irregular number of chromosomes in cells even when the checkpoint proteins appear to be functioning properly."

Draviam's co-authors are graduate students Irina Shapiro and Bree Aldridge and MIT Professor of Biology and Biological Engineering Peter Sorger.

Source: MIT

Explore further: UK court to rule on landmark 'pregnancy crime' case

add to favorites email to friend print save as pdf

Related Stories

Right place, right time: Cellular transportation compartments

Oct 26, 2014

Proteins are the machinery that accomplishes almost every task in every cell in every living organism. The instructions for how to build each protein are written into a cell's DNA. But once the proteins are constructed, they ...

Study supports DNA repair-blocker research in cancer therapy

Aug 17, 2009

Scientists at Dana-Farber Cancer Institute have uncovered the mechanism behind a promising new approach to cancer treatment: damaging cancer cells' DNA with potent drugs while simultaneously preventing the cells from repairing ...

Hibernating frogs give clues to halting muscle wastage

Jul 01, 2014

Scientists at the University of Queensland, Australia, have identified key genes that help burrowing frogs avoid muscle wastage whilst they are dormant. These genetic insights could help prevent muscle atrophy ...

Puzzling question in bacterial immune system answered

Jan 29, 2014

(Phys.org) —A central question has been answered regarding a protein that plays an essential role in the bacterial immune system and is fast becoming a valuable tool for genetic engineering. A team of researchers ...

Recommended for you

UK court to rule on landmark 'pregnancy crime' case

29 minutes ago

A British court is to rule on whether a woman committed a "crime of violence" against her child by drinking heavily during pregnancy, in a case that has raised concerns about criminalising mothers.

Expanding waistlines weigh heavy on Malaysia

49 minutes ago

Malaysians have a passionate love affair with their lip-smacking cuisine—rich curries, succulent fried chicken, buttery breads and creamy drinks—but it is increasingly an unhealthy relationship.

Global Ebola toll rises to 5,689: WHO

59 minutes ago

The World Health Organization said Thursday that the global death toll from the Ebola virus had increased to 5,689 out of a total of 15,935 cases of infection, mainly in western Africa.

Some people may be pre-wired to be bilingual

7 hours ago

(HealthDay)—Some people's brains seem pre-wired to acquire a second language, new research suggests. But anyone who tries to move beyond their mother tongue will likely gain a brain boost, the small study ...

User comments : 0

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.