Overexpression of spindlin1 induces metaphase arrest and chromosomal instability

Abstract

Spin/Ssty gene family is high conserved and very abundant transcript involved in gametogenesis, which was repeatedly detected in early embryo. Nevertheless, the biologic roles of the members are still largely unknown. Previously we have identified human gene spindlin1 as a homologue of the family from ovarian cancer cells, and reported that stable overexpression of spindlin1 could transform NIH3T3 cells and induce tumorigenesis in nude mouse. Here, we showed that spindlin1, as a nuclear protein, was relocated during mitosis. A fraction of spindlin1 proteins was dynamic distributed along mitotic spindle tubulin and enriched at midzone following anaphase entering. We also showed that transient overexpression of spindlin1 induced cell cycle delay in metaphase, caused mitotic spindle defects, and resulted in chromosome instability, micronucleus and multinuclear giant cells formation. Moreover, time-lapse microscopy revealed that these cells arrested at metaphase for more than 3 h with chromosome nondisjunction or missegregation. Furthermore, Mad2 up-regulation in these cells suggested that overexpression of spindlin1 may affect the bipolar spindle correctly attachment to chromosomes and activate spindle checkpoint. Taken together, these data demonstrated that excess spindlin1 protein may be detrimental for spindle microtubule organization, chromosomal stability and can potentially contribute to the development of cancer.