Two recent Notre Dame papers shed light on how breast cancer cells avoid death

Two new papers from the lab of Zach Schafer, Coleman Assistant Professor of Cancer Biology at the University of Notre Dame, offer insights into how breast cancer cells avoid anoikis, which is cell death induced by detachment from the extracellular matrix (ECM).

"Metastasis, the spread of cancer cells from the primary tumor site to distant sites in the body, is responsible for in excess of 90 percent of cancer deaths," Schafer said. "In order for cancer cells to metastasize, they must survive the trip from the primary tumor to a secondary site. A significant barrier to cancer cell survival is the process of anoikis. Cancer cells are periodically exposed to ECM detachment during metastasis, and thus it is critically important to better understand at the molecular level how cancer cells block anoikis. If we could better understand these molecular mechanisms, we could design novel chemotherapeutics aimed at inducing anoikis and thereby blocking metastasis."

The research described in the first paper describes how Schafer's lab group discovered that ErbB2, an oncogene overexpressed in approximately 30 percent of breast cancer patients, can block the induction of anoikis by causing multicellular aggregation. This multicellular aggregation results in stabilization of another protein, EGFR, that can signal in ECM-detached breast cancer cells to block anoikis.

"These findings suggest that finding ways to break up multicellular aggregates might be an effective strategy to eliminate metastasizing breast cancer cells," Schafer said. "In addition, targeting the EGFR protein has not been particularly effective in breast cancer patients, but our studies suggest that this may be a useful strategy to eliminate ECM-detached cancer cells."

The research was led by Raju Rayavarapu, a doctoral candidate in the Department of Biological Sciences under Schafer's supervision. Melissa Shaw, a junior biological sciences major, was a contributing author, and two former Notre Dame undergraduates, Brendan Heiden and Nicholas Pagani, also were co-authors. Additionally, Sydney Shuff, a high school senior at Concord High School in Elkhart, was a co-author and Siyuan Zhang, Nancy Dee Assistant Professor of Cancer Research at the Harper Cancer Research Institute, collaborated on the work.

The paper was featured as the cover article of the Journal of Biological Chemistry and can be accessed here. Kimbra Turner, a doctoral student in biological sciences at Notre Dame, designed the cover art.

What is advanced breast cancer?

Breast cancer is a type of cancer that starts to develop in the breast. Certain cells in the breast start to divide and grow in an uncontrolled manner, eventually forming a tumor, which may or may not be cancerous. Advanced breast cancer, also known as metastatic breast cancer or stage 4 breast cancer, is cancer that has spread from the breast to another part of the body. With advanced breast cancer, the cancer often spreads to the bones, lungs, liver, or brain.