prostate cancer discovery

Read About the Research You have Helped Make Possible.

the patrick c. walsh prostate cancer research fund

Studying the Molecular Switches for Metastasis

You may soon be hearing more about a protein called HMGA1. A tiny thing, it is nonetheless critical for rapid growth and development before birth. Normally, it is switched off or silenced in our cells after birth, but becomes abnormally flipped back on in aggressive cancer cells. During fetal development, it helps to maintain the structure and function of the cell's nucleus, its command post that houses our genetic material and directs the behavior and function of cells throughout our bodies. "Much like 23a quarterback on a football team, the nucleus tells the cell either to remain in place or move, or to progress into a more specialized position," explains molecular biologist Linda Resar, M.D. "The nucleus also dictates whether a cell will grow and divide, or remain quiescent."

In work supported by the Patrick C. Walsh Prostate Cancer Research Fund, Resar and co-investigators Robert Veltri and Karen Reddy are studying HMGA1 in prostate cancer. Resar's laboratory discovered that HMGA1 transforms normal cells into aggressive cancer cells. "Moreover, HMGA1 is a marker of poor outcomes for patients with diverse tumors," she says. "HMGA1 is present in high levels in aggressive prostate cancers, and it drives tumor cell invasion and aggressive behavior in animal models of cancer." Resar discovered that HMGA1 functions as a key molecular switch that cancer cells need to grow rapidly and spread. "Our preliminary studies suggest that HMGA1 alters nuclear shape and function to flip on genes that enable prostate cancer cells to leave their primary site, invade and metastasize."

Resar's laboratory discovered that HMGA1 transforms normal cells into aggressive cancer cells.

Resar and colleagues are conducting innovative studies to determine precisely how HMGA1 causes changes to the shape and function of the nucleus, "and whether we can use these alterations to predict which tumors will behave aggressively in men with prostate cancer. We will also uncover the genes and pathways that are turned on by the HMGA1 switch to transform normal prostate cells into invasive cancer cells." If the investigators can crack the code of how HMGA1 works, they will determine whether these changes can predict tumors that are likely to behave aggressively and move to distant sites. They also hope to develop approaches to target or block these changes in therapy. "Together, our team will define the role of HMGA1 in nuclear structure and function in prostate cancer," she says. "Results generated here will lay down the groundwork to determine whether HMGA1 and its role in nuclear reprogramming can be used to predict outcomes and optimize therapy for men with prostate cancer."

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