UNMC team gains insight into tumor progression, metastasis

Tony Hollingsworth, Ph.D

The research group led by UNMC’s Tony Hollingsworth, Ph.D., is known to tackle complex scientific problems.

Their latest discovery sheds light on how tumor cells interact and survive during the process of metastasis, when they end up in unusual environments (such as when a cell from the pancreas colonizes the liver).

The findings are reported in the Oct. 3 issue of The Journal of Biological Chemistry, a journal significant to the fields of biochemistry and molecular biology.

Understanding this newly discovered mechanism, Dr. Hollingsworth said, could help researchers discover new ways to influence the interaction and block the advantage it gives the tumor cell.

“This paper reports a lot of unique activities that were unexpected,” Dr. Hollingsworth said. “It helps us understand the way in which tumor cells utilize existing molecular systems in the body to their advantage, especially during metastasis of pancreatic tumor cells.

“It’s a very complex subject. We show a specific way in which a cell surface mucin molecule functions in morphogenetic signaling.”

MUC1 is a key modulator of several signaling pathways that affect tumor progression, motility and cell morphology. MUC1, the study found, interacted with and altered the function of p53, a tumor suppressor.

Dr. Hollingsworth’s team helped discover MUC1, a molecule that plays a role in the biology of pancreatic cancer, years ago. Since then, they have learned that it protects the cell surface and sends information about the cell surface to the nucleus.

The journal article further builds on their knowledge of the functions of the molecule. The results, Dr. Hollingsworth said, demonstrate that MET sends a signal to the nucleus by phosphorylating MUC1 and causing it to interact with p53, which in turn influences the growth and spread of tumors.

“In many ways, it is a reaction to the local environment that the tumor cell is in and that probably helps the tumor cell survive when it encounters an unusual environment. That’s how it helps tumor cells in metastasis.” Tony Hollingsworth, Ph.D.

The paper describes how MUC1 interacts with and is phosphorylated by MET, which is a receptor for hepatocyte growth factor (HGF). HGFs are known to be important for cancer progression and also affect cell motility.

“We documented the interaction between these two proteins (MUC1 and MET) and show a molecular mechanism by which that interaction functions,” Dr. Hollingsworth said. “The interaction between the two sends signals to the nucleus that change the transcriptional profile of a tumor cell.

“In many ways, it is a reaction to the local environment that the tumor cell is in and that probably helps the tumor cell survive when it encounters an unusual environment. That’s how it helps tumor cells in metastasis. Designing ways to block this process may help prevent metastasis.”

Visit the Journal of Biological Chemistry Web site to read the article titled “Phosphorylation of MUC1 by Met Modulates Interaction with p53 and MMP1 Expression.”

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