AUGUST 24, 2020, NEW YORK – Researchers led by Ludwig Chicago Co-director Ralph Weichselbaum and Ronald Rock of the University of Chicago have identified in preclinical studies a potential drug target for curtailing cancer metastasis.
Their study, published in the Proceedings of the National Academy of Sciences, describes how a compound named 4-hydroxyacetophenone (4-HAP) activates a specific protein motor in cells and so monkey-wrenches biomechanical processes essential to cell motility. It also demonstrates in a mouse model that targeting this protein motor undermines the metastasis of colon cancer cells.
“Metastasis is a major problem in cancer and accounts for about 90% of cancer deaths,” said Weichselbaum. “The overall goal here was to find something that reduces the metastatic burden to improve outcomes of cancer therapy.”
For a cancer cell to establish a metastatic growth, it must first break out of the tumor in which it resides, slip into a blood or lymph vessel, drift to a new region of the body, climb out of the vessel, creep into another organ and plant itself firmly in the new tissue. To do all that, it has to squeeze, wriggle and crawl through the molecular stuffing between the cellular layers of various tissues. Each step of metastasis thus requires a good deal of shape shifting, which is accomplished by molecular motors that reorganize the dynamic protein skeleton of the cell and drive the cellular protrusions—or lamellipodia—that enable its crawl.
