title: CCRK depletion inhibits glioblastoma cell proliferation in a cilium-dependent manner.
abstract: Loss of primary cilia is frequently observed in tumour cells, including glioblastoma cells, and proposed to benefit tumour growth, but a causal link has not been established. Here, we show that CCRK (cell cycle-related kinase) and its substrate ICK (intestinal cell kinase) inhibit ciliogenesis. Depletion of CCRK leads to accumulation of ICK at ciliary tips, altered ciliary transport and inhibition of cell cycle re-entry in NIH3T3 fibroblasts. In glioblastoma cells with deregulated high levels of CCRK, its depletion restores cilia through ICK and an ICK-related kinase MAK, thereby inhibiting glioblastoma cell proliferation. These results indicate that inhibition of ciliogenesis might be a mechanism used by cancer cells to provide a growth advantage.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Niina
authors.initials: N
authors.lastname: Roine
authors.forename: Tomi P
authors.initials: TP
authors.lastname: Mäkelä
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002923:Cilia / Q000201:enzymology* / Q000473:pathology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D034741:RNA, Small Interfering; C097276:CILK1 protein, human; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; C081931:MAK protein, human; D000095043:Cyclin-Dependent Kinase-Activating Kinase