SIK2 protein found to play a key role in ovarian cancer
The study, which focused on Salt Inducible Kinase 2 (SIK2), found that depleting SIK2 from ovarian cancer sensitized the cancer cells to paclitaxel and made the drug more effective in stopping the cancer's growth. Specifically, levels of SIK2 protein were increased in approximately 30% of ovarian cancers and were associated with poorer survival in women with the disease.
“There is a large window of opportunity to improve the effectiveness of existing chemotherapies by modifying the sensitivity of cancer cells to the drugs,” said Robert Bast, Jr., MD, vice president for translational research at The University of Texas MD Anderson Cancer Center. “In our search for proteins that are responsible for that sensitivity, we found that SIK2 was required for cell division and that its inhibition offers a novel approach to improving chemotherapy for ovarian cancer that deserves further study.”
When researchers Dr. Bast and Dr. Ahmed analyzed nearly 780 pools of siRNAs to identify proteins that alter sensitivity to paclitaxel, they found that SIK2 regulated sensitivity to paclitaxel. In addition, SIK2 was found to prevent division after doubling of DNA during proliferation of cancer cells.
“The discovery that SIK2 plays a role in cell cycle regulation is groundbreaking since to date it has been linked to cellular metabolism and energy balance,” concluded Ahmed Ashour Ahmend, MD, PhD, the study's first author and a member of the faculty at Oxford University. “In addition to improving the response of some cancer to taxane, our findings add support to emerging evidence that cancer cell metabolism and mitosis functions are coupled.”