January 25, 2016
Prostate Cancer Metastasis: New Discoveries
An, Yegnasubramanian and Haffner: Figuring out how cancer cells move through tissue and bone
One of prostate cancer's worst features is its ability to spread to distant sites, particularly bone, and to start new, malignant outposts. How do they do it? Research by scientists Srinivasan Yegnasubramanian, M.D., Ph.D., Michael Haffner, M.D., Ph.D., Steven An, Ph.D., and colleagues has turned up an important clue — and a potential new avenue for treatment.
"In order to invade other tissue and migrate far distances, cancer cells need to alter their cytoskeletal properties," says Yegnasubramanian. In other words, they need to become tiny shape-shifters. But exactly how they become malleable enough to move through tissue and bone has been poorly understood.
With support from the Patrick C. Walsh Prostate Cancer Research Fund and the David H. Koch Foundation, Yegnasubramanian, Haffner, An, and colleagues have identified a protein that appears to suppress the ability of normal cells to invade. This protein, called AIM1, "binds and modulates the major component of the cytoskeleton in normal prostate epithelial cells," Yegnasubramanian adds. They found that AIM1 seemed to have an out-of-body experience in invasive primary prostate cancer, separating itself from the cancer cell's cytoskeleton. "Additionally, AIM1 was often deleted and/or reduced in expression in metastatic prostate cancer." In laboratory models of prostate cells, when the scientists cut the expression of AIM1, the cancer cells began to remodel themselves, and "this increased their invasive and migratory potential. Taken together, these findings implicate the loss of AIM1 function in conferring prostate cancer cells with the ability to invade and produce invasive cancer and metastases."
This work continues, and now the investigators are working to identify the molecular mechanisms through which AIM1 can do its sleight-of-hand, allowing cancer cells to become invasive. "When we understand this, we may be able to prevent or treat prostate cancer metastases — the major cause of prostate cancer morbidity and mortality," says Yegnasubramanian. "We are also evaluating whether AIM1-mediated changes can be used as a biomarker to identify aggressive prostate cancers with metastatic potential."