Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

CK2 protein sustains colon cancer cells by sabotaging ability to commit suicide

24.02.2005


St. Jude study shows success in blocking CK2 activity in tumor cells, suggesting that a similar tactic could enhance treatment of patients with colorectal cancer and other solid tumors



A protein called CK2 plays a deadly role in colorectal carcinoma by blocking the ability of these tumors to activate a natural self-destruct mechanism that would clear this cancer from the body. This finding, by researchers at St. Jude Children’s Research Hospital, is currently published in the online edition of Oncogene. The renegade CK2 protein keeps the tumor alive and growing by desensitizing the cancer cells to the effects of another protein called TRAIL. Normally, TRAIL triggers apoptosis (cell suicide) in the cancer cells as a way of protecting the body. CK2 is an enzyme composed of four small proteins--two alpha proteins and two beta proteins.

The finding holds promise for developing drugs that help a patient’s cancer cells become sensitized to TRAIL-induced apoptosis. For example, treating the tumors with TRAIL to trigger apoptosis while blocking CK2 might enhance anti-cancer treatment for a variety of other solid tumors, such as pediatric rhabdomyosarcoma, according to Janet Houghton, Ph.D., a member of St. Jude Hematology-Oncology. Rhabdomyosarcoma is a tumor originating in cells that have some features of muscle cells.


The St. Jude team showed that CK2 exerts its anti-apoptosis effect within a structure called DISC (death-inducing signaling complex). The DISC is a large jumble of proteins that interact with each other after TRAIL binds to the outer cell membrane. After DISC forms, an enzyme called caspase-8 triggers the cascade of biochemical events outside DISC that eventually leads to cell death. By desensitizing the cell to TRAIL, CK2 disrupts the DISC response, which in turn prevents apoptosis and allows the cancer cell to continue growing. "The work my laboratory has done using our cell lines of colorectal cancer to investigate the role of CK2 in tumors is now bearing fruit," said Houghton, senior author of the Oncogene report. "We’ve shown in some detail how CK2 helps cancer cells survive the natural tendency for abnormal cells to self-destruct, as well as how to block CK2 and permit the cell to undergo apoptosis. In doing so, we’ve begun to map out a strategy for making cancer cells more likely to self-destruct."

The findings of the current study support and expand those published by Houghton’s laboratory last October in the journal Clinical Cancer Research. In that study, the team reported similar findings in rhabdomyosarcoma cells. In the current study using human colon carcinoma cells, the researchers found that while CK2 usually is continually active, they could block this activity using a CK2-inhibitor called DRB.

Subsequently, the team showed that blocking CK2 with DRB made the cells very sensitive to TRAIL, causing them to commit suicide. This proved the important role CK2 played in preventing TRAIL-induced cell suicide. However, DRB did not have an effect on normal cells, which strongly suggests that CK2 blocks apoptosis only in cancer cells.

Because DRB can also interfere with other cellular reactions, the researchers blocked CK2 using another technique: short hairpin RNA (sh RNA). This technique uses a tiny bit of genetic material specifically designed to shut down a particular gene--in this case, the gene for the alpha proteins that make up part of CK2. Again, CK2 activity was lost, the cancer cells were sensitized to TRAIL, and the cells committed suicide.

The researchers also showed that the ability of TRAIL to trigger apoptosis depended on caspase enzymes, such as caspase-8. Caspase enzymes are part of the biochemical pathway that triggers the cell to undergo apoptosis. Specifically, when the team added to the cancer cells a drug that blocks caspases, TRAIL-induced apoptosis was also blocked. "Our discovery that blocking CK2 makes cancer cells sensitive to TRAIL-induced cell suicide is very promising," said Kamel Izeradjene, Ph.D., a postdoctoral student in Houghton’s lab who did much of the work reported in Oncogene. "We hope to find effective drugs that block CK2 in samples of tumors removed from children treated at St. Jude."

"This is a translational research laboratory," Houghton said. "Our aim is to translate discoveries made here into better treatments for children with solid tumors."

Houghton currently collaborates on colorectal cancer treatment studies with physicians at the West Clinic in Memphis and is also working with a commercial firm to develop treatments for solid tumors based on her St. Jude work.

Other authors of the article are Leslie Douglas and Addison Delaney (St. Jude).

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht Tag it EASI – a new method for accurate protein analysis
20.06.2018 | Max-Planck-Institut für Biochemie

nachricht How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Creating a new composite fuel for new-generation fast reactors

20.06.2018 | Materials Sciences

Game-changing finding pushes 3D-printing to the molecular limit

20.06.2018 | Materials Sciences

Could this material enable autonomous vehicles to come to market sooner?

20.06.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>