Anoikis

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Anoikis is a form of programmed cell death that happens when cells that need to attach to their surroundings detach from the extracellular matrix (ECM). Normally, cells stay near the tissue they belong to because signals from nearby cells and the ECM help them survive. When cells lose those attachment signals, they may undergo anoikis.

Cancer cells can sometimes resist anoikis, which allows them to travel to other organs and form new tumors (metastasis).

The term was coined by Frisch and Francis in 1994. Anoikis literally means “a state of being without a home,” referring to the death that occurs when cell–matrix interactions are lost.

Some researchers have found that anisomycin can make metastatic cancer cells more sensitive to anoikis and reduce their spread, partly by lowering FLIP, a protein that blocks the cell’s death signals. Other studies show metastatic cells tend to have higher FLIP levels, and reducing FLIP with certain techniques or drugs can make them more likely to die when detached. This suggests that lowering FLIP could be a possible strategy to prevent cancer metastasis.

Cancer cells resist anoikis through several changes, including altered signals from integrins and the ECM, metabolic changes, and stress-response adaptations. A key part of this resistance involves disruption of pathways that control the NF-κB transcription factor.