Whole-genome screen identifies diverse pathways that negatively regulate ciliogenesis

We performed a high-throughput whole-genome RNAi screen to identify novel inhibitors of ciliogenesis in normal and basal breast cancer cells. Our screen uncovered a previously undisclosed, extensive network of genes linking integrin signaling and cellular adhesion to the extracellular matrix with inhibition of ciliation in both normal and cancer cells. Surprisingly, a cohort of genes encoding extracellular matrix (ECM) proteins was also identified. We characterized several ciliation inhibitory genes and showed that their silencing was accompanied by altered cytoskeletal organization and induction of ciliation, which restricts cell growth and migration in normal and breast cancer cells. Conversely, supplying an integrin ligand, vitronectin, to the ECM rescued the enhanced ciliation observed upon silencing this gene. Aberrant ciliation could also be suppressed through hyper-activation of the YAP/TAZ pathway, indicating a potential mechanistic basis for our findings. Our findings suggest an unanticipated reciprocal relationship between ciliation and cellular adhesion to the extracellular matrix and provide a resource that could vastly expand our understanding of controls involving “outside-in” and “inside-out” signaling that restrain cilium assembly.