All along the watchtower: is the cilium a tumor suppressor organelle?
Cilia or flagella have been around since almost the beginning of life, and have now developed specialized cell-type specific functions from locomotion to acting as environmental sensors participating in cell signalling. Genetic defects affecting cilia result in a myriad of pathological instances, including infertility, obesity, blindness, deafness, skeletal malformations, and lung problems. However, the consistency in which the common kidney cyst is coupled with cilia dysfunction has raised interest in the possibility that ciliary dysfunction might contribute to other neoplasms as well. A suite of recent papers convincingly linking cilia to hedgehog signalling, platelet-derived growth factor signalling, Wnt signalling and the von Hippel-Lindau tumor suppressor protein has rapidly expanded the knowledge base connecting cilia to cancer. We propose that these data support the notion of the cilium as a cellular Watchtower, whose absence can be an initiating event in neoplastic growth. Furthermore, we predict that we are just now seeing the tip of the iceberg, and that the list of cancers associated with altered ciliary signalling will grow exponentially in the next few years.
Mans
Dorus A
DA
Department of Medical Oncology, University Medical Center Utrecht, The Netherlands.
Voest
Emile E
EE
Giles
Rachel H
RH
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D002453:Cell Cycle; D049109:Cell Proliferation; D002923:Cilia / Q000235:genetics / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000503:physiopathology; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure*; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D006623:von Hippel-Lindau Disease / Q000378:metabolism
D002352:Carrier Proteins; D053823:Hedgehog Proteins; D051153:Wnt Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein