Featured Research

from universities, journals, and other organizations

A protein called cFLIP makes tumor cells in breast cancer resistant to treatments

Date:
December 14, 2010
Source:
University of Granada
Summary:
Researchers have found that cFLIP –- an inhibitor of death ligand-induced apoptosis –- is not only essential in breast tumor cells resistance to TRAIL treatments (a death ligand with a potent therapeutic potential against cancer), but this protein is also key to the survival of such cancer cells.

Researchers at the Andalusian Institute for Molecular Biology and Regenerative Medicine (CABIMER) and the University of Granada found that cFLIP -an inhibitor of death ligand-induced apoptosis- is not only essential in breast tumor cells resistance to TRAIL treatments (a death ligand with a potent therapeutic potential against cancer), but this protein is also key to the survival of such cancer cells.

Researchers proved that a variation in the expression of this protein may lead to the normal development of breast epithelium. This is an important finding to be considered in the design of cFLIP-targeted therapies against cancer.

This finding might very useful for scientists, that could design cancer therapies aimed at interfering the action of this protein. Such was the conclusion drawn by the researchers at the Andalusian Institute for Molecular Biology and Regenerative Medicine (CABIMER), in collaboration with the University of Granada.

The research conducted by Rosario Yerbes Cadenas, PhD candidate at the University of Granada, was led by professor Abelardo López Rivas, of CABIMER, and was aimed at analysing the potential of cFLIP inhibitors in cancer therapies.

At present, TRAIL is a death-ligand of the TNF family, with significant therapeutic potential against cancer, basically due to its ability to induce apoptosis in cancer cells without displaying significant toxicity toward normal cells. However, there are tumor cells that are resistant to TRAIL-induced apoptosis for unknown causes.

This study analysed the role of cFLIP in breast cancer cells' resistance to TRAIL-induced apoptosis. Thus, researchers concluded that cFLIP is key in these cells' resistance to TRAIL. Such conclusion was drawn from the evidence that the inhibition of their expression through treatments with Doxorubicin (anthracycline, widely used in chemotherapy) or with SAHA (Histone deacetylases inhibitor), as well as the silencing of its expression through cFLIP siRNA oligos (small interfering RNA), resulted in the sensitisation of breast cancer cells to TRAIL-induced apoptosis.

The authors of this research proved that cFLIP plays a survival role in tumorous and non-tumorous breast epithelial cells, since the inhibition of its expression induces apoptosis. This type of apoptosis requires the formation of the death-inducing signalling complex, which includes TRAIL-R2 receptor, adapter molecule FADD and procaspase-8- but is TRAIL-independent itself.

Conversely, in the light of the cFLIP relevance in controlling apoptosis, researchers studied the role of cFLIP in breast epithelial cells MCF-10A morphogenesis -a process where apoptosis plays an essential role. Thus, cFLIPL/cFLIPS overexpression inhibits lumen formation in acini from breast epithelial cells when they are cultured in a 3D extracellular matrix (3D cultures). Additionally, inhibition of cFLIP expression prevents the development of acini, since cells with low expression of cFLIP are unfeasible.

For this reason, regulation of cFLIP expression was very relevant to this research. Scientists determined that the PI3K/AKT signalling pathway is not the main responsible for cFLIP synthesis in breast cancer cell, but may be it is NF-kB pathway.

Additionally, this study revealed that the ubiquitin-proteasome system plays a key role in cFLIP cell degradation. At present, researchers are trying to identify E3-ubiquitin ligase protein, responsible for cFLIP degradation by such system.


Story Source:

The above story is based on materials provided by University of Granada. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yerbes R., Palacios C, Reginato MJ. and López-Rivas A. Cellular cFLIPL plays a survival role and regulates morphogenensis in breast epithelial cells. The Journal of Biological Chemistry, (in press)

Cite This Page:

University of Granada. "A protein called cFLIP makes tumor cells in breast cancer resistant to treatments." ScienceDaily. ScienceDaily, 14 December 2010. <www.sciencedaily.com/releases/2010/12/101214085845.htm>.
University of Granada. (2010, December 14). A protein called cFLIP makes tumor cells in breast cancer resistant to treatments. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2010/12/101214085845.htm
University of Granada. "A protein called cFLIP makes tumor cells in breast cancer resistant to treatments." ScienceDaily. www.sciencedaily.com/releases/2010/12/101214085845.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) — A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
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