Extrusion misregulation and cancer cell invason
One effect of unchecked cell extrusion is cancer invasion and metastasis. Using the transparent zebrafish embryonal skin as a model, we found that cells expressing an oncogenic KRas mutation—driver of pancreatic, colon, and lung cancers—are likely to extrude. However, instead of extruding apically out of the body, they are redirected. We call this process basal cell extrusion (BCE): cancer cells aberrantly extrude basally, back into the tissue that the epithelium encases. Surprisingly, the cancer cell sheds its apical membrane, along with surface epithelial traits, simultaneous with BCE, demonstrating a novel mechanical loss of epithelial identity. This endows invading KRas cells with new plasticity and allows differentiation into other cell types, reminiscent of stromal and neuronal cell populations in human pancreatic cancer.