Biology and Therapeutic Relevance of a Novel Kinase Pathway in Refractory Breast Cancers
Abstract
A particularly treatment-refractory subtype of breast cancer is the so-called triple negative breast cancer (TNBC). Our laboratory has recently identified a novel kinase, Ser/Thr kinase Stk36, which can regulate p63/p73 pathway in TNBC. Stk36 is overexpressed, genomically amplified, and subject to missense mutations in cancers including breast cancer. I therefore hypothesize that Stk36 is an endogenous apoptosis suppressor in TNBC whose overexpression and/or mutation may confer chemo-resistance. During the 1st funding year, I demonstrated that the apoptosis induced by Stk36 inhibition can be completely rescued by p73 ablation. P63 level and Hedgehog pathway activity are not involved in this process; p73 protein may translocate into more tightly chromatin-bound state (thus more transcriptionally active). In addition, overexpression of wildtype Stk36 confers modest resistance to cisplatin treatment in vitro.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA548848
Entities
People
- Lei He
Organizations
- Massachusetts General Hospital