Gamma-tubulin-containing abnormal centrioles are induced by insufficient Plk4 in human HCT116 colorectal cancer cells.
Cancer cells frequently induce aberrant centrosomes, which have been implicated in cancer initiation and progression. Human colorectal cancer cells, HCT116, contain aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. These cells also express unique centrosome-related structures associated with a subset of centrosomal components, including gamma-tubulin, centrin and PCM1. During hydroxyurea treatment, these abnormal structures become more abundant and undergo a change in shape from small dots to elongated fibers. Although gamma-tubulin seems to exist as a ring complex, the abnormal structures do not support microtubule nucleation. Several lines of evidence suggest that the fibers correspond to a disorganized form of centriolar microtubules. Plk4, a mammalian homolog of ZYG-1 essential for initiation of centriole biogenesis, is not associated with the gamma-tubulin-specific abnormal centrosomes. The amount of Plk4 at each centrosome was less in cells with abnormal centrosomes than cells without gamma-tubulin-specific abnormal centrosomes. In addition, the formation of abnormal structures was abolished by expression of exogenous Plk4, but not SAS6 and Cep135/Bld10p, which are downstream regulators required for the organization of nine-triplet microtubules. These results suggest that HCT116 cells fail to organize the ninefold symmetry of centrioles due to insufficient Plk4.
Kuriyama
Ryoko
R
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA. kuriy001@umn.edu
Bettencourt-Dias
Monica
M
Hoffmann
Ingrid
I
Arnold
Marc
M
Sandvig
Lisa
L
D002502:Centrioles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D045325:HCT116 Cells; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology; D015854:Up-Regulation
D014404:Tubulin; D050257:Tubulin Modulators; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases; D015739:Nocodazole; D006918:Hydroxyurea