Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation
Citations Over TimeTop 10% of 2013 papers
Abstract
Parkin, an E3 ubiquitin ligase well known for its role in the pathogenesis of juvenile Parkinson disease, has been considered as a candidate tumor suppressor in certain types of cancer. It remains unknown whether parkin is involved in the development of pancreatic cancer, the fourth leading cause of cancer-related deaths worldwide. Herein, we demonstrate the downregulation and copy number loss of the parkin gene in human pancreatic cancer specimens. The expression of parkin negatively correlates with clinicopathological parameters indicating the malignancy of pancreatic cancer. In addition, knockdown of parkin expression promotes the proliferation and tumorigenic properties of pancreatic cancer cells both in vitro and in mice. We further find that parkin deficiency increases the proportion of cells with spindle multipolarity and multinucleation. Parkin-depleted cells also show a significant increase in spindle misorientation. These findings indicate crucial involvement of parkin deficiency in the pathogenesis of pancreatic cancer.
Related Papers
- → Parkin is an E3 ligase for the ubiquitin-like modifier FAT10, which inhibits Parkin activation and mitophagy(2021)50 cited
- → Covalent ISG15 conjugation positively regulates the ubiquitin E3 ligase activity of parkin(2016)48 cited
- → The E3 Ubiquitin Ligase Parkin Is Recruited to the 26 S Proteasome via the Proteasomal Ubiquitin Receptor Rpn13(2015)38 cited
- → Parkin: Much More than a Simple Ubiquitin Ligase(2011)10 cited
- Potential Pathophysiological Crosstalk between Parkin andFBXO7 Signalling Pathways(2016)