Cell Adhesion Protects against Stress

In a study published Tuesday in Cell Reports, researchers found that cell-to-cell contacts are necessary for the survival of human cells under protein-damaging conditions and stress. They were surprised by the findings because the molecules they studied are usually linked with other cellular functions.

“Cell-to-cell contacts are essential for normal tissue functioning and mechanisms,” says senior author Lea Sistonen of Åbo Akademi University. “Cancer cells are known to utilize these contacts to form aggressive tumors and metastases. Our results show, indeed, that cancer cells become more vulnerable to drug treatment when their cell contacts are weakened.”

The research project focused on heat shock factor 2 (HSF2), a specialized gene-regulating protein, and its impact on cells’ capacity to survive protein-damaging stress. Protein-damaging stress can be caused by high temperatures, viral infections, and certain anti-cancer medications. The results showed that HSF2 contributes to protecting cells against stress by regulating those genes that mediate cell adhesion contacts.

The results were obtained by studying, among other things, how cancer cells respond to certain commonly used anti-cancer drugs. Cancer cells with impaired cell adhesion contacts were significantly less successful in surviving the drug treatment than the cells showing intact cell adhesion.

“Cell adhesion contacts are mediated by proteins known as cadherins, which serve as the source of message chains regulating cell death, but understanding of the molecular basis for these processes calls for further research,” Sistonen says. “Individual differences in these particular cell processes may partly explain why certain drugs work effectively for some patients but not for others.”