Suppression of protein critical to cell division stops cancer cells from dividing, kills them

December 08, 2011

Suppressing a newly identified and characterized protein involved in regulating cell division could be a novel strategy to fight certain cancers because it stops the malignant cells from dividing and causes them to die quickly, according to a study by researchers with UCLA's Jonsson Comprehensive Cancer Center.

During the five-year study, designed to seek new targets for anti-cancer therapies, researchers discovered that depleting the protein, called STARD9, also helped the commonly used chemotherapy drug Taxol to work more effectively against certain cancers.

Depletion of the protein did not work against all cancers, but it did show potential to be an effective way to battle certain types of melanoma and non-small cell lung cancers, said study first author Jorge Torres, a professor of chemistry and biochemistry and a Jonsson Cancer Center researcher.

"Biology and metabolism are different in cancer cells and check points that regulate normal cells are often misregulated in cancer, allowing the malignant cells to divide uncontrollably," Torres said. "Because of that, we set out to discover new cancer targets, and more specifically proteins critical for cancer cell division that we could potentially target with therapeutics."

The study appears today in the peer-reviewed journal Cell.

During cell division, cells form the microtubule-based mitotic spindle, a highly specialized and dynamic structure that aids in proper and equal chromosome transmission to the daughter cells, Torres said. One approach in the treatment of cancer has been to target microtubule dynamics or spindle assembly itself.

Torres and his team sought to identify and characterize proteins necessary for spindle assembly, and therefore vital to cell division. They performed a high throughput proteomic screen to find the proteins associated with the spindle and uncovered 592 proteins. It was unclear, however, if all the proteins were necessary for proper spindle function.

Next, they performed a high throughput genetic screen that knocked the proteins out one by one to see how that affected spindle function in the cells. They were looking for depletion of a protein that stopped cancer cell division and prompted the cells to die quickly.

"The idea was to find something that arrested the cells while they were trying to divide and injuring them in such a way that cell death occurred quickly," Torres said. "We were looking for a way to attack the cancer cells as they were dividing."

From the screens, Torres and his team selected the most promising protein whose depletion best interrupted cell division and resulted in the cells dying quickly and landed on STARD9, a kinesin-like protein - a sort of molecular motor - that functions to form a stable mitotic spindle.

Torres said there are some cancer clinical trials testing kinesin inhibitors, but so far they have not proved very successful. The inhibitors do stop cell division, but they don't damage the cell enough to induce a quick cell death and eventually the cells begin dividing again.

STARD9, however, not only arrests cells during division, it causes so much disruption in spindle formation and function that the cells die quickly. The cells, in effect, become too broken to repair themselves, Torres said.

"When STARD9 is depleted in the cancer cells, the chromosomes attempt to align for transmission into the daughter cells, but fail," he said. "They try for a while, but the chromosomes are being pulled apart from different directions and the DNA is tearing. In the end, their DNA condenses into a ball and the cells die."

Torres said researchers knew that STARD9 existed in cells from computational analyses, but no one had characterized its function until now.

The next step will be to confirm these findings in animal models by injecting mice with cancer cells and determining if depletion of STARD9 in these cells suppresses the formation of a tumor.

Torres is currently screening small molecules to find the ones that effectively inhibit STARD9s function. He's also conducting a molecular analysis of the protein and how it functions to form a proper spindle.

Finding a good STARD9 inhibitor could result in a new, less toxic combination therapy for certain cancers. Because depletion of the protein enhances the effectiveness of Taxol, Torres hypothesized that perhaps the chemotherapy drug, which causes many serious side effects, could be given in lower doses but perform just as well if used in combination with a STARD9 inhibitor.

"Our study highlights the utility of performing focused screens to understand cellular processes, as many of the genes we have identified as regulating mitosis (cell division) and apoptosis (cell death) were not identified in pervious genome-wide screens," the study states.
The study was funded in part by the National Institutes of Health, Genentech, the Leukemia & Lymphoma Society and the V Foundation for Cancer Research.

UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years. For more information on the Jonsson Cancer Center, visit our website at

University of California - Los Angeles Health Sciences

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 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