Are Diadenosine Polyphosphates and/or FHIT Involved in Anoikis?
Abstract
The FHIT (Fragile Histidine Triad) protein is an intriguing protein having certain properties of a tumor suppressor protein. The FHIT gene is altered in a large fraction of both sporadic and familial human breast cancers, genetically supporting its tumor gene status. Indeed, FRIT knockout mice have elevated frequency of various tumor types, consistent with this. The overexpression of the FHIT protein through recombinant adenovirus vector infection induces apoptosis and thus suppresses tumor growth, suggesting a more specific role for FRIT in apoptosis control. Yet, the biochemical activity and biologic function of PHIT protein are unknown at present, other than the fact that it binds and hydrolyzes the diadenosine polyphosphates Ap3A and Ap4A - molecules that accumulate in response to cellular stress. In this project we have focused on the potential role of FHIT in controlling one particularly cancer relevant apoptotic response - anoikis. Anoikis is the apoptotic response to cell-matrix detachment. It prevents mammary epithelial cells from colonizing in novel locations (i.e., metastasizing), thereby playing an important role in restricting mammary tumor progression that is often compromised in tumor cells. We have found that FHIT protein does not appear to play a role in anoikis, or, more generally, in apoptosis, prompting a re-examination of its actual cellular function. In the course of this project, however, we found a critical role for caspase-2 in anoikis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA424453
Entities
People
- Steven M. Frisch
Organizations
- Sanford Burnham Prebys Medical Discovery Institute