Understanding and Targeting Cell Growth Networks in Breast Cancer
Abstract
In this fourth annual review, we have demonstrated that translation plays a huge role in determining tumor initiation by oncogenes. We have found that the ARF tumor suppressor is translationally regulated by mTORC1 signals and that ARF in turn negatively regulates Drosha mRNA translation. This is important because loss of Drosha results in an inability to transform immortal cells with oncogenic RasV12 alleles. This implies that Drosha provides a pro- growth setting for future oncogenic events and that inhibiting Drosha function could be an important therapeutic avenue. We have also identified a second translational target of ARF: the DHX33 DEAD- box RNA helicase. Much like Drosha, ARF prevents DHX33 translation. DHX33 expression is required for efficient RasV12 translation, causing us to label ARF as a master regulator of oncogenic translation programs. Taken together, these insightful findings bring us significantly closer to our goal of understanding how signaling pathways impact major tumors suppressors in the control of cell growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2012
- Accession Number
- ADA563904
Entities
People
- Jason D Weber
Organizations
- University of Washington