SKA1 over-expression promotes centriole over-duplication, centrosome amplification and prostate tumourigenesis.
Although spindle- and kinetochore-associated protein 1 (Ska1) has previously been identified as essential for proper chromosome segregation, it is unknown whether it plays a role in tumour development. Here, we report that Ska1 over-expression promotes prostate tumourigenesis. Immunohistochemistry and quantitative RT-PCR analysis revealed that Ska1 was over-expressed in human prostatic intra-epithelial neoplasia (PIN), the most likely prostate cancer precursor, and adenocarcinomas. Up-regulation of Ska1 protein was also found to be tumour-specific in breast, lung and other common human cancers. Importantly, prostate-specific up-regulation of Ska1 in a transgenic mouse model resulted in spontaneous tumourigenesis. Furthermore, in addition to its abundance in spindle microtubules and the outer kinetochore interface during mitosis, Ska1 was enriched at centrosomes in cultured cells. Depletion of Ska1 caused a failure of centrosome duplication, whilst Ska1 over-expression led to centrosome amplification in human prostate epithelial cells via the induction of centriole over-duplication. These epithelial cells harbouring extra centrosomes switched from a non-tumourigenic to a tumourigenic state in nude mice. Taken together, these data indicate that Ska1 over-expression promotes tumourigenesis.
State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Centre, Shanghai Jiao Tong University, People's Republic of China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, People's Republic of China.
Jia
J
Li
Jim W
JW
Xuan
Vida
V
Khatamianfar
Fatma
F
Valiyeva
Madeleine
M
Moussa
Andrew
A
Sadek
Burton B
BB
Yang
Bai-Jun
BJ
Dong
Yi-Ran
YR
Huang
Wei-Qiang
WQ
Gao
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000502:physiology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D002868:Chromosomal Proteins, Non-Histone; C516427:SKA1 protein, human; C577106:Ska1 protein, mouse
centriole over-duplication; centrosome amplification; centrosome-associated protein; prostate tumourigenesis; spindle- and kinetochore-associated protein 1 (Ska1); transgenic mouse