Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells.

ABSTRACT:

Background

The KIAA1199 transcript is upregulated in colon adenomas and downregulated upon β-catenin knockdown.

Methods

Transcript profiling was performed on >500 colon biopsies, methylation profiling data were compared with transcript data. Immunohistochemistry assessed KIAA1199 protein expression in 270 stage II/III tumours (>3 years follow-up). The effects of stable KIAA1199 knockdown in SW480 cells (three different constructs) were studied using transcriptional profiling, proliferation and protein analysis.

Results

The KIAA1199 transcript was strongly upregulated in 95% of adenocarcinomas. Absent expression in normal mucosa correlated with KIAA1199 promotor methylation. Nuclear and cytoplasmic KIAA1199 protein expression was identified in colon adenocarcinomas and other types of cancers. A subpopulation of patients with tumours strongly expressing KIAA1199 in the nucleus showed a better outcome with regard to recurrence as lung or liver metastases. The KIAA1199 knockdown affected the cell cycle and the Wnt-signalling pathway. Reduced cellular proliferation and decreased KI67, phosphorylated retinoblastoma, β-catenin and ASCL2 protein expression supported these findings. Eighteen Wnt-signalling genes differentially expressed upon KIAA1199 knockdown correlated with the KIAA1199 expression profile in clinical specimens.

Conclusion

The KIAA1199 knockdown attenuates the effects of the Wnt/β-catenin signalling and it may thus be regarded as a regulatory part of this pathway.

SUBMITTER: Birkenkamp-Demtroder K 

PROVIDER: S-EPMC3170968 | biostudies-literature |

REPOSITORIES: biostudies-literature