SKA1 over‐expression promotes centriole over‐duplication, centrosome amplification and prostate tumourigenesis

Abstract

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.

SKA1 regulates actin cytoskeleton remodelling via activating Cdc42 and influences the migration of pancreatic ductal adenocarcinoma cells

“…SKA1 was reportedly increased as a candidate oncogene in several common human cancers, contributing to various steps of oncogenesis and poorer prognosis 14‐18 . Not only SKA1 genomic mutations result in chromosome congression failure and subsequent cell changes, 33 but also SKA1 overexpression itself is primarily responsible for oncogenic function.…”

Regulation of spindle and kinetochore‐associated protein 1 by antitumor miR‐10a‐5p in renal cell carcinoma

“…Several studies have indicated that SKA1 is involved in the growth and proliferation of various types of cancer, including oral adenosquamous and hepatocellular carcinoma, bladder cancer, gastric cancer, prostate cancer, thyroid cancer, non-small cell lung cancer, and glioblastoma. (44)(45)(46)(47)(48)(49)(50)(51) In the human genome, SKA1, SKA2, and SKA3 form the SKA complex. During mitosis, the SKA complex is localized between the outer kinetochore interface and the spindle microtubules.…”

E2F site in the essential promoter region does not confer S phase-specific transcription of the ABCC10 gene in human prostate cancer cells

“…The applied herein G 1 phase synchronization protocol differed from that applied in the case of LNCaP prostate cancer cells, by 7-hour longer growth in the regular media (Wang et al, 2016). The protocol applied in the case of S phase synchronization was analogous to those used by others (Chung et al, 2012;Li et al, 2014). The ABCC10 transcript was found to be expressed at a nearly identical level in asynchronous log-phase and S phase-synchronized CWR22Rv1 cell populations (Table 3).…”