Featured Research

from universities, journals, and other organizations

Likely culprit in spread of colon cancer identified

Date:
April 1, 2014
Source:
Washington University in St. Louis
Summary:
A poorly understood protein called PLAC8 has been implicated in the spread of colon cancer. While elevated PLAC8 levels were known to be associated with colon cancer, the researchers now have shown that the protein plays an active role in shifting normal cells lining the colon into a state that encourages metastasis.

Growing in three dimensional culture, colon cancer cells formed either smooth hollow structures (top) or spiky clumps (bottom). PLAC8 was highly expressed in the spiky clumps, which were shown to form rapidly spreading tumors in mice.
Credit: Cunxi Li, MD, PhD

New research at Washington University School of Medicine in St. Louis and Vanderbilt University Medical Center in Nashville has implicated a poorly understood protein called PLAC8 in the spread of colon cancer.

While elevated PLAC8 levels were known to be associated with colon cancer, the researchers now have shown that the protein plays an active role in shifting normal cells lining the colon into a state that encourages metastasis.

The work appears April 1 in the Journal of Clinical Investigation.

“We knew levels of this protein are elevated in colon cancer,” said co-author Lilianna Solnica-Krezel, PhD, professor and head of the Department of Developmental Biology at Washington University. “Now we’ve shown what PLAC8 could be doing -- causing the cells to transition to a state that allows them to spread.

“This discovery developed from a collaboration between my group studying zebrafish and Robert Coffey’s lab looking at human cells, both initially at Vanderbilt,” she said. “Since 2010, my group has continued the zebrafish work at Washington University.”

Senior author Robert Coffey, MD, the Ingram Professor of Cancer Research at Vanderbilt University, and his group have been developing new methods to grow colon cancer cells in three dimensions, rather than using typical procedures to grow cells in a flat dish.

Coffey’s group observed that colon cancer cells growing in three dimensions formed either smooth hollow balls or spiky clumps with protrusions extending into the surroundings. Compared to the smooth balls, the spiky clumps were shown to form rapidly spreading tumors in mice. When the researchers compared gene expression between the cells forming smooth balls and those forming spiky clumps, PLAC8 stood out. It was expressed at extremely high levels in the spiky clumps that formed aggressive tumors.

To gain a better understanding of PLAC8, Haiting Ma, PhD, a former graduate student in the Solnica-Krezel and Coffey labs, used a zebrafish model system to investigate the roles of this protein.

“We looked at this protein in zebrafish and saw that it was also expressed in the gut,” said Solnica-Krezel. “In normal zebrafish, PLAC8 is present on the inner lining of the gut. We also noticed PLAC8 is heavily expressed in the early embryos of zebrafish.”

Ma and his colleagues looked further into the developmental roles of PLAC8 and found that when there is too much of this protein, the zebrafish embryo developed abnormally, with slower cell movements resulting in an abnormal body shape and other developmental defects.

“We realized that these defects were very similar to abnormalities we see when the protein E-cadherin is mutated,” Solnica-Krezel said. “E-cadherin is a cell adhesion molecule present on the cell surface, which allows cells to stick to one another. The amount of E-cadherin on the surface is very important for cell movement, with too much or too little being detrimental to mobility.”

E-cadherin is also important in maintaining the sheet-like tissue structure called epithelium, which forms the inner lining of many organs, including the gut. Loss of E-cadherin can indicate a process known as epithelial-to-mesenchymal transition, where the cells detach, and the tissue loses its sheet-like nature, making it easier for the cells to migrate.

During early development, these transitions are normal, as cells must migrate to different parts of the developing organism and form new tissues and organs. But in cancer, this transition to more mobile cells can be the tipping point that causes them to break away from a tumor and invade neighboring tissues.

“Scientists know a lot about E-cadherin,” Solnica-Krezel said. “But this is the first link between PLAC8 and E-cadherin. Nobody knew that PLAC8 could regulate it. Too much PLAC8 causes E-cadherin levels to go down, and low E-cadherin is associated with abnormal cell movement.”

Moving full circle, first with human cells, then with zebrafish, the researchers returned to human tissues to investigate PLAC8 and associated proteins in colorectal tumors. They demonstrated that many markers of the epithelial-to-mesenchymal transition observed in zebrafish embryos with too much PLAC8 were also present at the edge of a human colon tumor.

Solnica-Krezel speculates PLAC8 could be an interesting target for future work in developing new cancer therapies.

“One could think about finding chemicals that might inhibit PLAC8’s activity,” she said. “But at present, this finding may have prognostic value. Those tumors expressing PLAC8 at high levels will be the most invasive.”


Story Source:

The above story is based on materials provided by Washington University in St. Louis. The original article was written by Julia Evangelou Strait. Note: Materials may be edited for content and length.


Journal Reference:

  1. Cunxi Li, Haiting Ma, Yang Wang, Zheng Cao, Ramona Graves-Deal, Anne E. Powell, Alina Starchenko, Gregory D. Ayers, Mary Kay Washington, Vidya Kamath, Keyur Desai, Michael J. Gerdes, Lila Solnica-Krezel, Robert J. Coffey. Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI71103

Cite This Page:

Washington University in St. Louis. "Likely culprit in spread of colon cancer identified." ScienceDaily. ScienceDaily, 1 April 2014. <www.sciencedaily.com/releases/2014/04/140401172912.htm>.
Washington University in St. Louis. (2014, April 1). Likely culprit in spread of colon cancer identified. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2014/04/140401172912.htm
Washington University in St. Louis. "Likely culprit in spread of colon cancer identified." ScienceDaily. www.sciencedaily.com/releases/2014/04/140401172912.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. 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