Abstract
AbstractIntegrating signals is essential for cell survival, leading to the concept of synthetic lethality. However, how signaling is integrated to control cell migration remains unclear. By conducting a “two-hit” screen, we revealed the synergistic reduction of cell migration when serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) were simultaneously suppressed. Single-cell analyses showed that STK40 knockdown reduced cell motility and coordination by strengthening focal adhesion (FA) complexes. Furthermore, STK40 knockdown reduced translocation of yes-associated protein (YAP) into the nucleus, while MAPK inhibition further weakened YAP activities in the nucleus to disturb FA remodeling. Altogether, we unveiled an integrated STK40-YAP-MAPK system regulating cell migration, and introduced “synthetic dysmobility” as a novel strategy to collaboratively control cell migration.One Sentence SummaryBlocking collaborative pathways within the integrated signaling network synergistically disrupts the migration of cells.
Publisher
Cold Spring Harbor Laboratory
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