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Continuous running, cancer cells from ovarian cells cease when deprived

  Lack of spontaneous ovarian cancer cells stop moving when deprived
Researchers from the University of Montreal Hospital Research Center (CRCHUM) Credit: CHUM

Did you know that 90% of cancer patients die from distant metastasis? The latter occurs when cancer cells are able to move in the patient's body and invade their healthy tissues. In a study published in Nature Communications researchers from the University of Montreal Hospital Research Center (CRCHUM) have shown the key role that a protein called Ran plays in the mobility of ovarian cancer cells. They showed that these cells cannot migrate from cancerous areas without the help of Ran.

Involved in cancer development and survival, Ran is often referred to as a transport protein that primarily supports transport between the inside of a cell and its nucleus. In ovarian cancer cells, the research group, led by Dr. Anne-Marie Mes-Masson and Dr. Diane Provencher, showed that Ran acts as a taxi to the cell membranes of another protein, RhoA, which is important in cell migration. 1

9659005] "In normal cells, RhoA can make its way directly to the cell membrane but in ovarian cancer cells it cannot. It must link to Ran first to reach the cell membrane. It really needs a ride," said Mes-Masson, researcher at CRCHUM, professor at Université de Montréal and member of the institute du cancer de Montréal. "In our study, we showed that in cancer cells where we inhibit the action of Ran, RhoA is broken. Without RhoA, cancer cells lose their ability to move, migrate and invade healthy tissues. "

Thanks to the great biochemistry expertise of the first author, Dr. Kossay Zaoui, the science team could explain at least in part why Ran is so important in a cancer cell. In many cancers, high expression of Ran is often associated with poor results.

"We have previously shown that Ran is a good therapeutic goal. Our study helps us understand when and in which cancer patients our approach can be most beneficial. cells do not need Ran to move around, we can target the cancer cells without touching the healthy cells. Based on our findings, it is likely that inhibitory Ran will also be a winning strategy in other cancers, Dr. Provencher, a researcher at CRCHUM, head of the Department of Gynecology oncology, professor at the Université de Montréal and a member of the institute du cancer de Montreal.

  Abnormal running, ovarian cancer cells stop moving when deprived
Simultaneous protein labeling: Ran (pink) and tubulin (green) in ovarian cancer cells. The majority of Ran is in the nucleus, but our study shows that some of it is located on the surface of cells that induce ovarian cancer movement and invasion via its partner RhoA Credit: Euridice Carmona, CRCHUM

The researchers have already begun to develop small molecules that can inhibit Ran and test them in the preclinical models they have developed to show that they can slow down or eliminate cancer development. One day they hope that these new drugs will enter the clinic to be used to treat ovarian cancer patients.

The importance of our biobank

For three decades, Drs. Provences and Mes-Masson have collaborated to create the largest biobank for ovarian cancer samples from women who have agreed to participate in their research program. They were able to develop and characterize cell lines from tumor tissues, and these cell lines were important for performing this work.

These cell lines are now used by ovarian cancer research groups worldwide to perform ovarian cancer research. The patient's valuable contribution to research gives rise to the type of new discoveries that both scientists hope will help to cure this fatal disease.

According to the Canadian Cancer Association, 2,800 Canadian women with ovarian cancer were diagnosed in 2017 and 1800 died of the disease. It is the fifth leading cause of death in North America.

A "one-two punch" for drying out cancerous ovarian cells

More information:
Kossay Zaoui et al. Ran promotes membrane alignment and stabilization of RhoA to orchestrate ovarian cancer cell invasion, Nature Communications (2019). DOI: 10.1038 / s41467-019-10570-w

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Ovarian cancer cells continue to migrate as they are deprived due to running (2019, July 10)
July 10, 2019
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