Researchers discover what cancer cells need to travel

Feb 22, 2012 By Carly Hodes
An invasive cancer cell moves with its leading edge.

(PhysOrg.com) -- Cancer cells must prepare for travel before invading new tissues, but new Cornell research has found a possible way to stop these cells from ever hitting the road.

Researchers have identified two key proteins that are needed to get cells moving and have uncovered a new pathway that treatments could block to immobilize and keep cancer from spreading, said Richard Cerione, Goldwin Smith Professor of Pharmacology and at Cornell's College of Veterinary Medicine.

The study, co-authored by graduate student Lindsey Boroughs; Jared L. Johnson, Ph.D. '11; and Marc Antonyak, senior research associate, is published in the (286:37094-37107).

Most stay stationary, but the ability for some to move helps embryos develop, wounds heal and immune responses mobilize. When migrating cells go astray they can cause developmental disorders, ranging from cardiovascular disease to mental retardation. Metastasis (the spread of cancer from one part of the body to another) also relies on cell migration. How exactly cancer cells migrate and invade tissues continues to be a mystery. However, Cerione's lab uncovered a potentially important clue when it noticed that cancer cells gearing up to move would collect a protein called tissue transglutaminase (tTG) into clusters near the .

A migrating cervical cancer cell stained for tissue transglutaminase (green). Cells must gather this protein at their leading edge in order to move.

"tTG is turning up in many aspects of research and seems to be contributing to the process that turns cells cancerous," said Cerione. "Lindsey and Marc discovered that cells must gather tTG into a specific place in their membrane before they can move. But tTG is usually inactive, and we've been trying to understand how a cell gets this protein to the exact right place so that it can be activated to stimulate cell migration."

Observing in culture, Cerione's lab found a missing link in our understanding of : become hyperactive invasion vehicles by using tTG together with other proteins like wheels, poking them through the surface to form a "leading edge" that pulls the cell forward. But to get the wheels to the leading edge, it turns out they need another protein to roll them there -- a "chaperone" protein called heat-shock-protein-70 (Hsp70).

Researchers discover what cancer cells need to travel
A diagram illustrates the process of metastisis.

"We've known for years that Hsp70 acts as a chaperone to other proteins, ensuring that they assume the right structure and behave properly when a cell is under stress," said Cerione. "Heat shock proteins have also been implicated in cancer, although scientists have been trying to understand their exact role in cancer. Our research has uncovered a previously unknown role for these chaperones -- helping tTG get to the leading edge. tTG must be in this location for cancer to spread."

When cells become stressed, Hsp70 influences the behavior of their "client" proteins, ensuring they keep the right shape. Cells need chaperones like Hsp70 to ensure that various proteins work correctly and don't warp, but these same chaperones can help cancer cells spread by helping move tTG to the membrane surface. Using inhibitors that block the function of chaperones, Cerione and his team paralyzed Hsp70s and stopped cells in culture from gathering tTG into a leading edge, effectively immobilizing them.

Exactly how Hsp70 gets tTG going remains unknown, but Cerione believes other proteins are involved.

"If we can better understand how Hsp70 influences tTG, we can figure out ways to modulate that interaction to immobilize and keep them from becoming invasive," said Cerione. "We suspect Hsp70 is using a third kind of protein to move tTG, and that's what we're trying to figure out now. Finding the next link in this chain of events could have important consequences for preventing cancer migration and metastasis."

This work was funded, in part, by the National Institutes of Health.

Explore further: A refined approach to proteins at low resolution

Related Stories

New study says molecule can starve cancer cells

Sep 17, 2010

While overcoming an addiction is usually the healthy choice, cancer cells' addiction to the amino acid glutamine is key to their vitality and growth. But Cornell researchers have discovered a molecule that ...

Researchers give mutants another chance

Feb 11, 2009

Researchers at Fox Chase Cancer Center have demonstrated that it might be possible to treat genetic diseases, including some forms of cancer, by "rescuing" the misshapen, useless proteins produced by some mutant genes.

Green plant transport mystery solved

Jan 26, 2010

Contrary to prevailing wisdom, a new study from plant biologists at UC Davis shows that proteins of the Hsp70 family do indeed chaperone proteins across the membranes of chloroplasts, just as they do for other cellular structures.

Recommended for you

A refined approach to proteins at low resolution

Sep 19, 2014

Membrane proteins and large protein complexes are notoriously difficult to study with X-ray crystallography, not least because they are often very difficult, if not impossible, to crystallize, but also because ...

Base-pairing protects DNA from UV damage

Sep 19, 2014

Ludwig Maximilian University of Munich researchers have discovered a further function of the base-pairing that holds the two strands of the DNA double helix together: it plays a crucial role in protecting ...

User comments : 0