# Planar cell polarity pathway contribution to breast cancer metastasis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $351,955

## Abstract

The planar cell polarity (PCP) pathway plays central roles in embryonic development by mediating cellular
motility events required for proper tissue structuring. Accumulating evidence suggests that the PCP pathway is
exploited by some solid tumors to promote their invasiveness and metastatic potential. Likewise, the epithelial-
mesenchymal transition (EMT) is a cellular program widely engaged during development whereby cells lose
their epithelial character, including apico-basal polarity and cell-cell interactions, and gain migratory and
invasive properties to take on a more mesenchymal stem cell nature. It is well established that solid tumor cells
engage EMT in the initiation of metastasis. The purpose of the proposed studies is to examine on a molecular
level the link between these two developmental pathways, to discern the degree to which an EMT-PCP axis
contributes to the motility and invasiveness of both non-transformed and transformed breast cells, and to
unravel a novel molecular mechanism contributing to the suppression of the PCP pathway. We hypothesize
that EMT inducers engage the Vangl-dependent planar cell polarity pathway to promote the motility and
invasiveness of both non-transformed and transformed breast epithelial cells, and to promote breast cancer
metastasis. Aim 1 will first examine the extent to which EMT induction in breast cells regulates components of
the PCP pathway, and then assess whether key components of the PCP pathway are required for EMT-
induced breast cell motility and invasiveness. A subset of Aim 1 studies will also attempt to discern whether
PCP signaling regulates EMT. Aim 2 will examine a novel PCP negative regulatory mechanism in detail,
exploring the hypothesis that the Vangl-associated E3 ubiquitin ligase Nrdp1 suppresses PCP signaling by
mediating the K63 polyubiquitination of Dvl family proteins in breast epithelial and cancer cells. Aim 3 will
examine whether the core PCP component Vangl2 contributes to breast cancer metastasis using genetically-
engineered and orthotopic transplant mouse models of basal breast cancer. The successful completion of
these studies will uncover a novel connection between two developmental programs that are reactivated by
tumor cells in promoting malignancy, and will assess the contribution of this synergistic interaction in promoting
breast cancer malignancy.

## Key facts

- **NIH application ID:** 10372001
- **Project number:** 5R01CA230742-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** KERMIT L CARRAWAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $351,955
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372001

## Citation

> US National Institutes of Health, RePORTER application 10372001, Planar cell polarity pathway contribution to breast cancer metastasis (5R01CA230742-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10372001. Licensed CC0.

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