Investigating Fn14 As A Driver Of Breast Cancer Metastasis

Project Objective
The presence of a protein called Fn14 on the surface of 75% of invasive breast cancers, has been shown to be strongly prognostic for distant metastasis, with the strongest association in HER2/neu positive and Triple Negative breast cancers. Fn14 is not present in normal breast tissues, but once expressed, is sufficient to trigger cell invasion, and behaviour consistent with metastatic progression. This project aims to define the utility of F14 an independent prognostic indicator for aggressive disease, with therapeutic vulnerability in a breast cancer cohort and in time to validate it as a driver of metastasis in preclinical models.  Invasion and metastasis are the major reasons for breast cancer-associated mortality.

This study showed that aberrant Fibroblast Growth Factor Inducible 14 (Fn14) protein expression has strong clinical significance in HER2+ and TNBC as a significant independent prognostic indicator predicting Distant Metastasis Free Survival (DMFS) in breast cancer. Currently, no publications have reported the prognostic utility of Fn14 and so these are novel findings. The findings support a recommendation that future targeted approaches to inhibit Fn14 signaling in TNBC tumours harboring an oncogenic KRAS mutation, should avoid use of anti-Fn14 monotherapy.

The team intend to validate these findings utilizing tissue from the Mayo Clinic.

HOST INVESTIGATOR: University of Otago