Abstract
KIBRA is a regulator of the Hippo-yes-associated protein (YAP) pathway, which plays a critical role in tumorigenesis. In the present study, we show that KIBRA is a positive regulator in prostate cancer cell proliferation and motility. We found that KIBRA is transcriptionally upregulated in androgen-insensitive LNCaPC4-2 and LNCaP-C81 cells compared to parental androgen-sensitive LNCaP cells. Ectopic expression of KIBRA enhances cell proliferation, migration and invasion in both immortalized and cancerous prostate epithelial cells. Accordingly, knockdown of KIBRA reduces migration, invasion and anchorage-independent growth in LNCaP-C4-2/C81 cells. Moreover, KIBRA expression is induced by androgen signaling and KIBRA is partially required for androgen receptor signaling activation in prostate cancer cells. In line with these findings, we further show that KIBRA is overexpressed in human prostate tumors. Our studies uncover unexpected results and identify KIBRA as a tumor promoter in prostate cancer. Deregulation of the Hippo signalling pathway is implicated in human cancers. Dong and colleagues now report that KIBRA, a scaffold protein that regulates Hippo signalling, promotes prostate cancer cell proliferation and motility. They find that KIBRA is transcriptionally upregulated in androgen-insensitive prostate cancer cell lines, and that KIBRA expression is induced by androgen receptor signalling. Overexpression of KIBRA enhances cell proliferation, migration and invasion, whereas KIBRA knockdown reduces motility and anchorage-independent growth. The authors also report that KIBRA is overexpressed in human prostate tumours, revealing a potential pro-tumorigenic role for this protein.
Original language | English (US) |
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Pages (from-to) | 1800-1811 |
Number of pages | 12 |
Journal | FEBS Journal |
Volume | 283 |
Issue number | 10 |
DOIs | |
State | Published - May 1 2016 |
Keywords
- AR signaling
- KIBRA
- motility
- proliferation
- prostate cancer
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology