Weber receives grant to study cancer growth

Studying the cancer cell cycle may lead to a better understanding of how to control — and possibly inhibit — cancer growth.

Jason Weber, Ph.D., assistant professor of medicine and of cell biology and physiology, recently received a five-year, $1.3 million grant from the National Institute of General Medical Sciences to study a protein called nucleophosmin (NPM), which may have a role in promoting tumor growth.

“NPM appears to be able to transform cells and is expressed in many different cancers, especially in breast cancer,” said Weber, a Siteman Cancer Center researcher.

While healthy cells are equipped with mechanisms that limit cell division, cancerous cells have genetic damage that results in uncontrolled cell growth and multiplication. A tumor is an accumulation of these abnormal cells.

The most common type of genetic damage, found in approximately half of all tumors, results in mutation of the p53 tumor suppressor protein, followed closely by the loss of another tumor suppressor protein referred to as ARF (p14 in humans and p19 in mice).

“ARF is like a circuit breaker,” Weber said. “It’s part of a signaling network within the cell that responds to stress. Cancer cells try to disable this network.”

Weber’s work centers on understanding how ARF impedes abnormal signals that cause cells to reproduce too often. The p53-ARF tumor suppressor pathway already is under close scrutiny. For example, ARF has been found to enable p53 to curb cell division or to initiate cell death if it detects stressful conditions.

Further studies with mice show that ARF itself has the ability to suppress tumor formation, independent of p53. A section of ARF called the amino terminus is required for normal cell cycle arrest in the absence of p53. NPM appears to bind to the amino terminus of ARF and has been linked to processes such as growth control and protein synthesis.

“Cancer cells produce a large amount of protein, and NPM can shut down protein synthesis,” Weber said. “But we don’t yet know whether this behavior is a cause or a consequence of cell growth inhibition.”

With this new grant, Weber’s team will be studying NPM to elucidate its role in the alternate ARF tumor suppression pathway. Clarifying NPM’s function involves understanding its relationship with ARF, NPM’s movement capabilities within the cell, and the consequences of missing NPM.