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A cell’s primary cilia function like antennae. Operating like a 24/7 news outlet, these hairlike structures are present on the surface of all animal cells, where they receive signals or information from the outside environment and deliver them inside the cell. Researchers in the lab of Sergio Gradilone, PhD, professor at The Hormel Institute, University of Minnesota, have discovered that these primary cilia have a connection to an important information delivery system known as the epidermal growth factor receptor (EGFR) signaling pathway.

This EGFR pathway sends a signal to the cell and triggers it to grow and divide. Then, the cell’s receptor is destroyed or degraded, which removes the signal and prevents the cell from further growth and division. Capitalizing on this connection could lead to more effectively treating diseases such as polycystic liver disease or cholangiocarcinoma, as well as broader applications for other cancer types.

“What we discovered is that in normal cells, the receptors need to first move, or translocate, to the primary cilia, and from there, it’s degraded. When you have tumor cells or different cells that have defects in primary cilia, that translocation is not happening. So, the receptor remains active for a longer time, and is telling the cell to keep growing,” Gradilone said.

This continued cell growth can result in cancerous and polycystic cells multiplying at uncontrolled, uninterrupted rates.

This work by the Gradilone research group has been published in a paper appearing in the scientific journal Hepatology, which explores the relationship between a cell’s primary cilia and this EGFR process that stimulates cells to grow and divide. While this study focuses primarily on bile duct cells and has possible treatment applications for diseases such as cholangiocarcinoma and polycystic liver disease, there are broader possible applications for other cancer types as well, such as breast, prostate, and colon cancers, which also experience primary cilia loss.

When a normal cell transforms into a tumor cell, it loses primary cilia. EGFR overexpression and active mutations are commonly found in different tumors—but if there were an alternative approach to cause the destruction of the EGFR receptor, that could lead to significant developments in designing more effective treatments for cancer and polycystic diseases.

A therapeutic approach known as “ciliotherapy” would involve inhibiting the activity of EGFR by putting cilia back in tumor cells where they belong.  The Gradilone researcher group’s discoveries tied to the EGFR signaling pathway offers exciting new insights that further describe this important role that cilia play in stopping the EGFR signal.

“We now have more knowledge about how tumor cells remove the cilia. So we can stop that process, put the cilia back, and now, the cell’s primary cilia is acting in a normal way. So we terminate the uncontrolled growth signal that is coming from the receptor,” Gradilone said.

The study publication, titled “Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling,” was authored by Gradilone research group members Kishor Pant PhD, Seth Richard, Estanislao Peixoto, PhD, and Subheksha Baral, in collaboration with researchers at Mayo Clinic and Northwestern University Feinberg School of Medicine.