Cell extrusion

Various factors such as apoptosis,[1] overcrowding,[4] pathogens[6] and replicative stress[2] can trigger extrusion from epithelia.

Additionally, cells transformed with oncogenic mutations such as HRAS[7] and Src can be ejected from epithelia by a similar extrusion process called Epithelial Defense Against Cancer (EDAC).

[15] Cells transformed with KRas, a driver of pancreatic, and some types of lung and colon cancer, have unregulated autophagy, which degrades S1P and prevents apical extrusion.

[5] Rescue of S1P2 alone is sufficient to reduce orthotopic pancreatic cancer and metastases in a mouse model.

When epithelia experience pathological crowding, as airway epithelial do during an asthma attack, they can extrude at such high rates that it destroys the barrier they should provide.

[16] This then mechanically causes the ensuing inflammation and hyper-susceptibility to infections that can follow an asthma attack.