By Lynn Adams
With their faster-than-normal growth, cancer cells can burn through resources quickly, sometimes leaving their surroundings empty of needed nutrients. Mei Kong, Ph.D., wants to know how cancer cells survive when the nutrients are gone, and how to turn that survival skill against them.
|Mei Kong, right, discusses results with lab member Wen-I Wang. (Photo by p.cunningham)|
Kong recently joined City of Hope as an assistant professor in the Division of Tumor Cell Biology.
“Cancer cells face two distinct metabolic challenges: how to acquire nutrients to support their growth and how to survive temporary periods when supply is low,” Kong said. Her data suggest that a protein called protein phosphatase 2A, or PP2A, plays a role.
PP2A can modify other proteins as part of a process called phosphorylation, which cells use to adapt to changes in their environment.
In phosphorylation, cells control key proteins involved in cell growth, maintenance and death by attaching or removing chemical pieces called phosphate groups.
Two sets of enzymes control phosphorylation: kinases, which add phosphate groups, and phosphatases, which remove them.
Faulty phosphorylation is common in cancer cells. “Most scientists focus on kinases; however, the role of phosphatases is largely unknown. It is a wide-open field,” Kong said.
As tumors develop, their rapid growth and limited blood supply often lead to conditions where nutrient levels fade. Researchers currently do not know how tumor cells survive these periods of stress. If they can unveil the mechanisms, they might exploit the knowledge to kill the cancer cells.
Kong began studying PP2A as a postdoctoral fellow at the University of Pennsylvania’s Abramson Family Cancer Research Institute. She and her colleagues sought to understand how PP2A regulates apoptosis, a type of programmed cell death.
Cancer cells commonly use inhibition of apoptosis as a survival strategy.
In work published in the journal Science, Kong and her team found that a subunit of PP2A, called alpha4, is necessary for PP2A to inhibit apoptosis.
Their further work found that alpha4 is important for cell migration, which affects cancer metastasis, and that alpha4 is required for the overall stability and activity of PP2A.
Kong’s short-term goal is to understand how alpha4 and PP2A regulate cancer cell survival during nutrient deprivation. Once this is known, researchers may be able to design cancer drugs that target the PP2A complex and short-circuit this survival mechanism.
Because the PP2A complex is common to many cancers, Kong hopes her work will benefit a large population of cancer patients. She also aims to investigate different protein phosphatases to understand how they function during tumor development.
Kong earned her doctoral degree at McGill University in Montreal, Canada, where she was on the Dean’s Honor List for Outstanding Doctoral Thesis and Graduate Career.