Exploiting the compromised spindle assembly checkpoint function of tumor cells: dawn on the horizon?
Aneuploidy is a frequent property of cancer cells that arises as a consequence of chromosomal instability (CIN). A major safeguard mechanism protecting cells from CIN is the spindle assembly checkpoint. This checkpoint surveys proper attachment of chromosomes to the mitotic spindle and effectively suppresses erroneous chromosome segregation by delaying mitotic progression until proper spindle-chromosome interactions have been established. Several lines of evidence suggest that the development of aneuploidy may be a gradual process that in many cases could result from subtle spindle checkpoint defects that occur during tumorgenesis and steadily weaken spindle checkpoint function. Here we discuss the evidence for this concept and address the question whether normal somatic cells and tumor cells could perhaps exhibit differences in spindle checkpoint regulation that allow the design of more specific anti-tumor strategies that effectively kill tumor cells but spare normal cells.
Schmidt
Marc
M
Department of Dermatology, University Medical Center Mannheim, Mannheim, Germany.
Medema
René H
RH
D000818:Animals; D002453:Cell Cycle; D043171:Chromosomal Instability / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008941:Spindle Apparatus / Q000378:metabolism* / Q000473:pathology*