Page 28 - The Hormel Institute 2024 Annual Report

28 | THE HORMEL INSTITUTE
// UNIVERSITY OF MINNESOTA
Our lab, Cancer Cell Biology and Transla- tional Research, is dedicated to under- standing the biological processes that
lead to cancer, with a special focus on the role of primary cilia in tumor biology. Primary cilia are tiny, hair-like structures that protrude from the cell surface, acting as cellular antennas to sense and transmit signals from the environment.
We are investigating how the loss of these organelles in tumor cells contributes to cancer progression and how restoring cilia can poten- tially revert cells to a more normal state. Our ultimate goal is to develop new therapeutic strategies by restoring ciliary function in cancer cells, particularly in aggressive cancers like cholangiocarcinoma.
KEY RESEARCH FINDINGS
This year, we published a significant study in Hepatology titled ”Cholangiocyte Ciliary Defects Induce Sustained Epidermal Growth Factor Receptor Signaling”. Our research reveals a novel mechanism by which ciliary defects lead to prolonged Epidermal Growth Factor Receptor
Our findings illuminate the molecular pathways involved in cholangiocyte proliferation regulated by primary cilia. Ciliary defects have been described in many other tumors, further increasing the significance of our research.
(EGFR) signaling in cholangiocytes, contributing to both polycystic liver diseases and cholangio- carcinoma (bile duct cancer).
Polycystic Liver Diseases (PLD) are rare genetic disorders characterized by chronic liver dysfunc- tion, cyst formation, and fibrosis, leading to liver enlargement and complications due to the abnor- mal proliferation of cholangiocytes (bile duct cells).
Cholangiocarcinoma is an aggressive form of cancer that arises from the epithelial cells of the bile ducts. It is a lethal malignancy with limited treatment options and a median survival of
only 24 months. Its incidence has increased significantly, highlighting the urgent need for new therapeutic strategies.
EGFR is a protein that helps cells grow and divide. However, when EGFR signaling becomes uncontrolled due to ciliary defects, it can lead to excessive cell proliferation and cancer progres- sion. Our study shows that the inability of EGFR to migrate to primary cilia results in persistent activation, underscoring the role of cilia as tumor suppressors.
We discovered that using HDAC6 inhibitors can restore ciliary function and accelerate EGFR degradation, reducing abnormal signaling.
This suggests that pharmacological restoration of primary cilia could be a promising strategy for treating EGFR-driven pathologies in liver diseases like PLD and cholangiocarcinoma.