Eph on - eph off: insights into molecular switches that (mis) guide cancer cell positioning

摘要

Eph RTKs together with membrane-bound ephrins are cell guidance cues that relay spatial information by modulating cell-cell adhesion and detachment. Their developmentally-regulated signaling underlies major patterning programs, while their unscheduled function is implicated in disease progression of invasive cancers. During Eph-guided positioning Eph cells translate ephrin abundance on interacting cells into fine-tuned cellular responses. In cancers, emerging evidence suggests that type and disease stage may determine if Eph/ephrin interactions promote or prevent tumour progression and metastasis: EphB2/EphB3 signalling acts tumour suppressive in colon cancer, while mutated EphA3 seems to play a prominent role in colon and lung cancer, melanoma and glioblastoma. Ephs, unlike other RTKs, elicit cellular responses even if their kinase is silenced and interaction with ephrin cells results in adhesion: It is the capacity to support or suppress Eph kinase signaling which dictates if Eph and ephrin cells respond with segregation or intermingling and invasion.