# Pathways that regulate basal and metastatic phenotypes in triple negative breast cancers

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $33,905

## Abstract

The current studies are a supplement to a proposal on what regulates basal and
metastatic phenoytpes in triple negative breast cancer (TNBC) with a focus on the function of
the insulin-like growth factor type 1 receptor (IGF-1R). The proposed supplementary research
project will extend studies related to Aim 1 of the parent grant that were designed to investigate
the interaction between the IGF-1R and the Wnt signaling pathway. Our recent analysis of the
human breast cancer database revealed an inverse correlation Wnt2 and its receptor, Frizzled 9
(Fzd9), and IGF-1R expression. Moreover, in Wnt-driven mouse mammary tumors with reduced
IGF-1R signaling leading to a metastatic phenotype, we also identified increased Wnt2 and
Fzd9 expression. Wnt2 is the prominent Wnt ligand for Fzd9, and this signaling loop follows the
canonical Wnt pathway wherein Wnt2 binding to Fzd9 increases the levels of total β-catenin.
Expression of Wnt2 and Fzd9 are elevated in several different kinds of cancer including breast,
and Wnt2 promotes the development of a more invasive, metastatic cancer phenotype in breast
and colorectal tumor cells. Our preliminary data further confirm that Fzd9 is upregulated in the
human luminal epithelial MCF7 breast cancer cell line after inhibiting IGF-1R. Wnt2 expression
has been reported in cancer-associated fibroblasts (CAFs); our preliminary data show that some
human breast cancer cells also express Wnt2 in addition to Fzd9 suggesting this signaling loop
can act in both a paracrine and autocrine manner. Taken together, the data provide the basis for
our new hypothesis that reduced levels of IGF-1R in breast cancer leads to increased activation
of the Wnt2/Fzd9 signaling loop. This will be tested by the following two specific aims:
1) Determine how the Wnt2/Fzd9 signaling axis is regulated by reduced IGF-1R signaling and
define the cellular components responsible for Wnt2 expression.
2) Investigate how the Wnt2/Fzd9 signaling axis alters tumor cell phenotype in the context of
reduced IGF-1R function.

## Key facts

- **NIH application ID:** 10059304
- **Project number:** 3R01CA204312-04S1
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Teresa L Wood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,905
- **Award type:** 3
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10059304

## Citation

> US National Institutes of Health, RePORTER application 10059304, Pathways that regulate basal and metastatic phenotypes in triple negative breast cancers (3R01CA204312-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10059304. Licensed CC0.

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