UCLA researchers target protein and kill cancer cells

After a five year study, researchers at UCLA’s Jonsson Comprehensive Cancer Center have found the depletion of the START domain-containing protein 9 (STARD9 for short), has the potential to help with the efficacy of the common chemotherapy drug Taxol against certain cancers.

Though it is known that cancer is a fatal, life-altering disease, the knowledge behind causes of cancer is somtimes sparse. There are several known and speculated causes of cancer such as genetic inheritance, heavy smoking, sunlight overexposure, radiation, environmental toxins, etc.

As far as cells, they have a variety of lifespans, though none last forever. All normally functioning cells experience apoptosis, a preprogrammed termination. When apoptosis fails, a cancerous cell is born.

Cancerous cells, because they are not regulated, exhibit abnormal growth that forms tumors. Some very dangerous tumors are able to travel throughout the bloodstream and interrupt different bodily functions.Since the discovery of cancer, countless studies have been conducted to understand and to find a cure for cancer.

As small as cells are, they utilize a very sophisticated system to undergo cellular division, also referred to as mitosis. In the M phase of mitosis, the mitotic spindle is responsible for dividing the duplicated chromosomes into the two separate daughter cells. The mitotic spindle was a main focus of the research that lead to the discovery of STARD9's potential uses.

According to Jorge Torres, a researcher at Jonsson Cancer Center and professor of chemistry and biochemistry at UCLA, the mitotic spindle aids in the correct chromosome transmission to the daughter cells. An approach taken in the treatment of cancer is direct targeting of the microtubles dynamics or the spindle assembly.

"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.’

Through the use of a high-throughput proteomic screen, 592 proteins associated with spindle activity were identified, though it was unclear whether every single one was directly involved. The researchers tested every protein one by one to analyse how they influenced the mitotic spindle. Using a high-throughput genetic screen to test the proteins one by one, researchers discovered that removal of one protein in particular, STARD9, significantly stopped cell division.

"The idea was to find something that arrested the cells while they were trying to divide and injured 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." The depletion of this protein was shortly followed by cell death.

The presence of STARD9 in cells had always been known. However it’s function was a mystery until now. Further research is being conducted to find an inhibitor for the protein STARD9.

Jorge Torres hypothesizes the discovery of an effective STARD9 inhibitor can be grounds for an innovative, less toxic combination therapy for specific cancers.