Researchers have identified a signaling pathway that transforms epithelial cells into aggressive tumor cells

A specific signaling pathway called TNF-α controls the transformation of epithelial cells into aggressive tumor cells. During cancer progression, cells activate their own TNF-α-related program and become invasive, writes News Medical Life Sciences.

An international research team led by Ataman Sendoel from the Institute for Regenerative Medicine at the University of Zurich found that the specific signaling program acts not only as a general driver of clonal expansion in human epithelia such as skin and mucous membranes of the esophagus, bladder or colon.

To find out why only certain clones of epithelial cells end up turning into malignant tumors, the researchers took a detailed look at epithelial cancers such as squamous cell cancer, the second most common malignant skin tumor. They developed a CRISPR method for single-cell analysis that allowed them to document clonal expansion throughout epithelial tissue with single-cell precision. This is the largest study of its kind to provide a systematic view of how mutations in cancer genes alter cell behavior.

“We focused on the 150 most frequently mutated cancer genes in epithelial tumors and followed their fate during clonal expansion and cancer formation in each cell type by analyzing all active genes,” notes the scientist. The researchers identified a specific program of TNF-α (tumor necrosis factor alpha), a signaling pathway that plays a crucial role in inflammation and cell communication. During clonal expansion in normal epithelia, TNF-α signaling is provided by the environment involving immune cells such as macrophages and promotes the proliferation of cells that have accumulated mutations in cancer genes. Once these cells accumulate too many driver mutations, their malignant transformation begins - and a tumor begins to develop.

According to the researchers, understanding the differences and similarities between clonal expansion in normal tissues and tumors may lead to the development of new strategies for early detection, prevention and treatment of these types of tumors.

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