Featured Research

from universities, journals, and other organizations

How signals trigger cancer cells to spread

Date:
May 25, 2014
Source:
Albert Einstein College of Medicine of Yeshiva University
Summary:
A signaling pathway in cancer cells that controls their ability to invade nearby tissues in a finely orchestrated manner has been discovered by researchers. The findings offer insights into the early molecular events involved in metastasis, the deadly spread of cancer cells from primary tumor to other parts of the body.

This electron micrograph shows a cancer cell (upper darker area) that has formed three invadopodia that are penetrating the adjacent extracellular matrix (lower lighter area).
Credit: Jose Javier Bravo-Cordero/Albert Einstein College of Medicine

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a signaling pathway in cancer cells that controls their ability to invade nearby tissues in a finely orchestrated manner. The findings offer insights into the early molecular events involved in metastasis, the deadly spread of cancer cells from primary tumor to other parts of the body. The study was published today in the online edition of Nature Cell Biology.

To migrate from a primary tumor, a cancer cell must first break through surrounding connective tissue known as the extracellular matrix (ECM). The cancer cell does so by forming short-lived invadopodia--foot-like protrusions these cells use to invade. Invadopodia release enzymes that degrade the ECM, while other protrusions pull the cancer cell along, much like a locomotive pulls a train. The invading cancer cell relies on the cycle of invadopodium formation/disappearance to successfully travel from the tumor and enter nearby blood vessels to be carried to distant parts of the body.

"We've known for some time that invadopodia are driven by protein filaments called actin," said study leader Louis Hodgson, Ph.D., assistant professor of anatomy and structural biology at Einstein. "But exactly what was regulating the actin in invadopodia was not clear."

Previous studies had suggested that a protein called Rac1 played a role in cancer-cell invasion. When Rac1 levels are elevated, cancer cells display more invasive characteristics. But this suspected Rac1 activity in invadopodia had never been directly observed, only indirectly inferred.

To surmount this hurdle, Dr. Hodgson and his colleagues in the Gruss Lipper Biophotonics Center at Einstein devised a new fluorescent protein biosensor that, combined with live-cell imaging, revealed exactly when and where Rac1 is activated inside cancer cells.

Using this biosensor in highly invasive breast cancer cells taken from rodents and humans, the Einstein team discovered that when an individual invadopodium forms and is actively degrading the ECM, its Rac1 levels are low; on the other hand, elevated Rac1 levels coincide with the invadopodium's disappearance. "So high levels of Rac1 induce the disappearance of ECM-degrading invadopodia, while low levels allow them to stay -- which is the complete opposite of what Rac1 was thought to be doing in invadopodia," said Dr. Hodgson.

To confirm this observation, the researchers used siRNAs (molecules that silence gene expression) to turn off the RAC1 gene, which synthesizes Rac1 protein. When the gene was silenced, ECM degradation increased. Conversely, when Rac1 activity was enhanced -- using light to activate a form of the Rac1 protein -- the invadopodia disappeared.

In subsequent experiments, the Einstein team deciphered other parts of the Rac1 signaling cascade during invasion and showed that this signaling mechanism is regulated differently in normal breast epithelial cells.

"Rac1 levels in invadopodia of invasive tumor cells appear to surge and ebb at precisely timed intervals in order to maximize the cells' invasive capabilities," said Dr. Hodgson.

Most of the 580,000 U.S. cancer deaths each year are caused by complications from the spread of cancer to distant tissues and organs, rather than from the primary tumor itself. So throwing a monkey wrench into the inner workings of invasive tumor cells -- perhaps with a drug that prevents them from locally activating or inhibiting Rac1 -- could be extremely useful.

"Rac1 inhibitors have been developed," Dr. Hodgson said, "but it wouldn't be safe to use them indiscriminately. Rac1 is an important molecule in healthy cells, including immune cells. So we'd need to find a way to shut off this signaling pathway specifically in cancer cells."


Story Source:

The above story is based on materials provided by Albert Einstein College of Medicine of Yeshiva University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yasmin Moshfegh, Jose Javier Bravo-Cordero, Veronika Miskolci, John Condeelis, Louis Hodgson. A Trio–Rac1–Pak1 signalling axis drives invadopodiadisassembly. Nature Cell Biology, 2014; DOI: 10.1038/ncb2972

Cite This Page:

Albert Einstein College of Medicine of Yeshiva University. "How signals trigger cancer cells to spread." ScienceDaily. ScienceDaily, 25 May 2014. <www.sciencedaily.com/releases/2014/05/140525154722.htm>.
Albert Einstein College of Medicine of Yeshiva University. (2014, May 25). How signals trigger cancer cells to spread. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2014/05/140525154722.htm
Albert Einstein College of Medicine of Yeshiva University. "How signals trigger cancer cells to spread." ScienceDaily. www.sciencedaily.com/releases/2014/05/140525154722.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com
Google's Next Frontier: The Human Body

Google's Next Frontier: The Human Body

Newsy (July 27, 2014) Google is collecting genetic and molecular information to paint a picture of the perfectly healthy human. Video provided by Newsy
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.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

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