Austin, Minn. — A team of researchers led by Professor Ningling Kang, PhD, at The Hormel Institute, University of Minnesota, has published an article in the scientific journal Cellular and Molecular Gastroenterology and Hepatology (CMGH). The paper, entitled “PKMζ, a brain-specific PKCζ isoform, is required for glycolysis and myofibroblastic activation of hepatic stellate cells,” details how hepatic stellate cells, found in the liver, play a role in liver metastasis in patients with colorectal cancer (CRC). Better understanding of processes such as the one the Kang lab discovered play a crucial role in developing more effective cancer treatments for patients.
Colorectal cancer is the second most common cause of cancer deaths and is expected to claim over 53,000 lives in the United States in 2024 alone, according to the American Cancer Society. Colorectal cancer metastasizing or spreading to the liver is a major contributing factor for the high death rates among colorectal cancer patients.
The Kang lab’s research project explored how hepatic stellate cells, found in the liver, are converted into cancer-associated fibroblasts (CAFs). CAFs are cells that can be found in connective tissue and play an important role in wound healing, but can also contribute to liver metastasis in CRC.
Previously, the Kang lab discovered that in order for hepatic stellate cells to be converted into CAFs, they require energy sourced from breaking down glucose. In this study, the research team studied how Glut1, a protein that helps move glucose across the cell membrane and into the cell, gets anchored to the cell surface for glucose transport in hepatic stellate cells.
They learned that the process is controlled by a particular signaling pathway in the cell. That pathway involves a chain reaction of events from a lipid called sphingosine-1-phosphate (S1P), protein kinase M zeta (PKMζ), and a protein called vasodilator-stimulated phosphoprotein (VASP).
“The finding opens doors for drug development for the prevention and treatment of CRC liver metastasis,” said Dr. Kang.
The study also revealed a peculiar finding about PKMζ. Thought to be a brain-specific isoform or protein variant that plays a role in long-term memory maintenance in the brain, this study is the first to confirm it is also expressed in hepatic stellate cells in the liver, and that it is required for glucose metabolism and for converting these cells into fibroblasts that fuel cancer metastasis.
Authors of the paper include Dr. Kang and The Hormel Institute Associate Professor Gaspar Kitange, MD, PhD, as well as Xianghu Wang, Yuanguo Wang, Bing Bai, Aurpita Shaha, and Wenming Bao, all of whom have served as researchers in Dr. Kang’s lab.