Cancer Cells Spread When They Stop Recycling Waste

Credits; TheScientist

Cells perpetually produce mountains of waste, such as damaged proteins or haywire organelles, but they have evolved a sustainable recycling plan to prevent trash piles. Autophagy is an essential waste disposal process that salvages used parts for resources that the cell can reuse. Scientists are exploring how autophagy affects the growth of tumor cells, but few studies have focused on its role in metastasis.

Publishing in Cell Reports, researchers identified a long-overlooked autophagy regulator that stops breast cancers from crossing tissue boundaries. By studying variation in this gene, scientists may one day leverage it to predict metastases in cancer patients.

Although recycling benefits the environment, autophagy has a more nuanced effect on cancer. Previous studies revealed that some autophagy genes either protect against or exacerbate tumors. “However, there are a large number of other genes that impact or regulate autophagy that have not been systemically examined,” said Jun-Lin Guan, a cell biologist at the University of Cincinnati and study coauthor. Moreover, researchers primarily examined how autophagy factors control the primary tumor. “There were relatively few investigations looking at metastasis specifically,” Guan noted.

Guan and his team compared 171 genes that influence autophagy to study how they affect metastasis in a mouse model of breast cancer. By using clustered regulatory interspaced palindromic repeats (CRISPR)-CRISPR-associated protein (Cas9) knock-out screens, they systematically deleted each gene to see if its absence allowed tumors to spread unchecked.

Out of 171 autophagy-regulating genes, they identified a few dozen that curbed metastasis. In their absence, tumor cells spread to the lung, an organ to which this cancer type doesn’t typically venture. The gene that codes for p47 protein produced the biggest difference when depleted, suggesting that it plays a key role in curbing breast cancer metastasis. “Previously, it was unknown that it could affect cancer,” Guan remarked.



By Kamal Nahas, PhD

Article can be accessed on: The Scientist