National Cancer Institute 5F30CA294624-03

Dissecting the Role of TRPV1 in Triple-Negative Breast Cancer Innervation

The award funds research to study how TRPV1 contributes to nerve growth in triple-negative breast cancer, aiming to find new ways to reduce cancer metastasis by targeting nerve infiltration.

Description

This project aims to uncover mechanisms by which breast cancer cells attract sensory nerves into tumors, potentially enabling new therapeutic targets to reduce metastasis and improve survival. The project focuses on TRPV1, a non-selective cation channel on sensory nerves that promotes neurite outgrowth. Preliminary data suggest that TNBC cells promote sensory neurite outgrowth via TRPV1 activation, leading to increased c-Jun and IL6 expression. The hypothesis is that TNBC secretions stimulate TRPV1, activating c-Jun and genes involved in neurite outgrowth, driving nerve infiltration into tumors. The research includes three specific aims: Investigate the role of c-Jun and IL6 in sensory neurite outgrowth in 2D; Use a 3D hydrogel model to study effects of TNBC cells on neurite outgrowth and TRPV1's role; Examine TRPV1's role in recruiting nerves into tumors in vivo using genetic and pharmacologic inhibition. Successful completion will provide insights into nerve-cancer interactions and suggest new clinical strategies to inhibit metastasis.

View original record