Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer.
Defects in the spindle assembly checkpoint are thought to be responsible for an increased rate of aneuploidization during tumorigenesis. Despite a plethora of information on the correlation between BUB-MAD gene expression levels and defects in the spindle checkpoint, very little is known about alteration of another important spindle checkpoint protein, Cdc20, in human cancer and its role in tumor aneuploidy. We observed overexpression of CDC20 in several oral squamous cell carcinoma (OSCC) cell lines and primary head and neck tumors and provide evidence that such overexpression of CDC20 is associated with premature anaphase promotion, resulting in mitotic abnormalities in OSCC cell lines. We also reconstituted the chromosomal instability phenotype in a chromosomally stable OSCC cell line by overexpressing CDC20. Thus, abnormalities in the cellular level of Cdc20 may deregulate the timing of anaphase promoting complex (APC/C) in promoting premature anaphase, which often results in aneuploidy in the tumor cells.
Mondal
Gourish
G
Human Genetics and Genomics Division, Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Kolkata-700 032, India.
Sengupta
Shiladitya
S
Panda
Chinmoy K
CK
Gollin
Susanne M
SM
Saunders
William S
WS
Roychoudhury
Susanta
S
D064173:Anaphase-Promoting Complex-Cyclosome; D000782:Aneuploidy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D064199:Cdc20 Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D043171:Chromosomal Instability; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008938:Mitosis; D008940:Mitotic Index; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D008941:Spindle Apparatus; D014162:Transfection; D014407:Tumor Cells, Cultured; D043743:Ubiquitin-Protein Ligase Complexes
C534699:CCNB1 protein, human; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; C577488:CDC20 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome