Research says blocking a motor protein can stop breast cancer cells

Dynein

Dynein is a motor protein that helps cells move along tiny tracks called microtubules. The researchers discovered that dynein is also responsible for powering the movement of breast cancer cells in soft tissue models that mimic the human body.

The study, published in the journal Advanced Science, shows that by blocking dynein, the cancer cells become paralyzed and unable to migrate. This could offer a new way to prevent metastasis and improve the chances of survival for breast cancer patients.

According to Erdem Tabdanov, a lead co-corresponding author on the study and assistant professor of pharmacology at Penn State, the findings are groundbreaking in multiple aspects. He explains that dynein’s involvement in cancer cell motility is a new discovery and that targeting dynein could be an effective way to prevent the spread of cancer cells.

The study was a collaboration between Penn State’s Department of Chemical Engineering and College of Medicine, as well as researchers from the University of Rochester Medical Center, Georgia Institute of Technology, Emory University, and the U.S. Food and Drug Administration.

The researchers used live microscopy to observe the movement of live breast cancer cells in two different systems. The first system was a two-dimensional network of collagen fibers, which represents the extracellular matrix that surrounds tumors. The second system was a three-dimensional network of microscopic hydrogel particles or microgels, which simulate soft tissue.

In both systems, the researchers found that dynein was essential for the movement of cancer cells. When they inhibited dynein with drugs or genetic tools, the cancer cells became stuck and unable to move.

Amir Sheikhi, an assistant professor of chemical engineering and biomedical engineering at Penn State, discovered that dynein is crucial for the invasion of cancer cells using three-dimensional models that resemble a tumor. This breakthrough suggests a new strategy for managing cancer that involves stopping the cancer cells from moving instead of killing them with radiation or chemotherapy, which can also damage healthy cells. This is a promising development because it means that destroying the cells is not necessary, only halting their movement.

Tabdanov explained that paralyzing the cancer cells could be a better strategy than chemotherapy, which tries to kill the cancer cells faster than they can damage the body. Chemotherapy can also cause side effects such as hair loss, nausea, and fatigue.

“Chemotherapy is like a race against time,” Tabdanov said. “It causes a lot of collateral damage to the body’s normal tissues while it is fighting the cancer. If we can contain the cancer, stop it from spreading, we can preserve the health of the body.”

The researchers cautioned that their findings are still preliminary and must be tested in human or animal trials before they can be applied to clinical practice. Sheikhi has filed several patents related to his team’s platform and plans to use it to study other diseases besides cancer.

Study abstract:

The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin-driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein-generated forces is identified. These forces arise within a non-stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein-powered locomotion becomes indispensable during invasive3D migration within a tissue-like luminal network formed by spatially-confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.