Cell-Suicide-Gene Linked To Metastasis

November 12, 1997

REHOVOT, Israel - November 13, 1997 - A Weizmann Institute of Science study reported in the November 13 issue of Nature provides new evidence for a recent theory about the development of metastasis.

According to this theory, one of the factors contributing to metastasis -- the spread of cancer from the site of the primary tumor to other body organs -- is a loss of a mechanism by which cells "commit suicide."

In the new study, Weizmann researchers demonstrate that a cell- suicide gene called DAP-kinase can prevent metastasis. This finding suggests that a loss or malfunction of this gene allows metastasis to develop.

"In our experiment, we have shown that introducing a 'good' copy of DAP-kinase into metastatic cells restores the ability of these cells to follow the order to kill themselves," says research team leader Prof. Adi Kimchi of the Weizmann Institute's Molecular Genetics Department.

"It's important, however, to remember that this gene is only one of many factors involved in the development of metastasis, so that much research still needs to be conducted before we can find molecular ways to block this life-threatening process," she says.

Kimchi conducted the study with doctoral students Boaz Inbal and Ofer Cohen, as well as with Prof. Lea Eisenbach and Ezra Vadai of the Weizmann Institute's Immunology Department, and Drs. Sylvie Polak-Charcon and Juri Kopolovic of the Sheba Medical Center in Tel Hashomer.

When cells 'refuse' to die The DAP-kinase gene was discovered and isolated by Prof. Kimchi's team some two years ago. This gene was known to be involved in cell "suicide," also referred to as programmed cell death or apoptosis.

Cell death is essential for the proper renewal and turnover of tissues. But when cells "refuse" to die after they have finished performing their function -- for example, because the DAP-kinase gene is lacking or doesn't function properly -- the result can be unwanted cell proliferation and development of cancerous tumors.

Prof. Kimchi hypothesized that apart from contributing to the development of primary tumors, the lack or malfunctioning of DAP-kinase can also cause cancerous cells to break off from a tumor and set out to spawn metastases. Formation of metastases is the most dangerous stage in cancer.

Kimchi and colleagues found that in metastatic tumor lines DAP-kinase indeed is not functioning. To test their hypothesis further, they "engineered" DAP-kinase into cells removed from metastatic tumors in mice, and returned these cells into the laboratory animals. The result: the molecular activity that could lead to the formation of metastases ceased inside these cells.

This finding supported the notion that when the cells contain a normal, functioning copy of the DAP-kinase gene, they obey the signals that instruct them to die during the different stages of metastasis.

In contrast, when the gene is not doing its job the cell disobeys the "suicide" command, and this disobedience may result in metastasis.

Prof. Kimchi holds the Helena Rubinstein Chair of Cancer Research, and Prof. Eisenbach, the Georg F. Duckwitz Chair of Cancer Research.

This research was supported by QBI Ltd. and the Israel Ministry of Science.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. It's 2500 scientists, students, technicians and engineers pursue basic research in the quest for knowledge and enhancement of the human condition. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are high priorities.

American Committee for the Weizmann Institute of Science

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.