Galectin-3 represses cancer cell death

Researchers know that human cancer cells avoid the normal cell-death pathway, called apoptosis, and instead continue to thrive, often spreading to other sites in the body. They don’t know, however, how these cells circumvent apoptosis.

Hyeong-Reh Kim, PhD, associate professor of pathology, believes a glycoprotein called galectin-3 may be an important piece of the puzzle. “My laboratory, in collaboration with Dr. Avaraham Raz at Karmanos, recently found that galectin-3 is a novel regulator of apoptosis,” Dr. Kim said, reporting that the galectin-3 has been associated with many human tumor cells, including breast cancer.

With a three-year $300,000 grant from the Department of Defense, Dr. Kim and her research group will specifically study the molecular mechanisms by which galectin-3 regulates the apoptotic cell death pathway during metastasis. She explained, “Normal cells will undergo apoptosis by either detaching from the extracellular matrix, which is a complex network of macromolecules, or by losing cell-cell contact. Cancer cells, however, bypass the death pathway and become resistant to cell death signaling. They are then able to travel through the bloodstream and metastasize to a second site.” She believes that galectin-3 somehow enhances the cell’s survival during metastasis.

By studying the death pathway regulated by galectin-3, she said, “We hope to provide new insights into enhancing cancer cell death.” This basic understanding might ultimately have both therapeutic and diagnostic applications, she noted. “This may lead to the development of new reagents to induce apoptosis in breast cancer cells and may contribute to the understanding of the role of galectin-3 in metastasis.”

In addition to this grant, Dr. Kim has two other funded projects – one from the National Institutes of Health and another from the Department of Defense – both related to cell death. Under these projects, she is investigating the roles of platelet-derived growth factor and the bcl-2 gene family in apoptosis regulation in breast cancer.