Accession Number:

AD1095373

Title:

Viral Infection as a Secondary Driver of Aggressive Breast Cancer Growth and Metastasis

Descriptive Note:

Technical Report,30 Sep 2015,29 Sep 2018

Corporate Author:

Washington University St. Louis United States

Personal Author(s):

Report Date:

2018-12-01

Pagination or Media Count:

10.0

Abstract:

In the antiviral setting, type I IFN induction is predominantly triggered through the activation of cytosolic receptors that recognize double-stranded RNA dsRNA. The dsRNA sensor retinoic acid-inducible gene I RIG-I contains a C-terminal DExDH box RNA helicase domain which interacts with viral dsRNA. Its activation triggers downstream signaling cascades that lead to type I interferon production. In this report, we show that in a p53 deficient setting, upon ARF loss, the canonical type IIFN pathway is activated. In our year 1 report, we demonstrate the critical role of RIG-I in regulating the induction of interferon-beta and its downstream activation of ISG15 expression. Moreover, we show that RIG-I is absolutely required for the enhanced proliferation and cellular transformation properties observed in cells lacking p53 and ARF. This work will be impactful to all breast cancer research trying to understand the relevant pathways that might imbue aggressive properties to tumor cells. This is a significant series of findings due to our ability to identify a novel pathway involved in tumor aggressiveness.

Subject Categories:

  • Medicine and Medical Research
  • Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE