# TGFbeta-regulated epithelial-mesenchymal transition (EMT)

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $355,038

## Abstract

Abstract
Aggressive tumors that are metastatic and intrinsically resistant to conventional therapies represent a critical
issue mediating the morbidity and mortality of most, if not all tumors, including breast cancer. It is postulated
that targeting the epithelial-mesenchymal transition (EMT) and the ensuing formation of cancer stem cells
(CSCs) is likely to represent a means of reducing the rate at which primary breast cancers spawn metastatic
derivatives. In the context of cancer, cells having undergone an EMT have enhanced tumor-initiating ability,
are capable of generating mammospheres, exhibit cell-surface markers and gene expression profiles similar
to both normal mammary (MaSC) and breast cancer (BCSC) stem cells and become more resistant to
chemotherapeutics. We have recently demonstrated a role for TGFβ-induced EMT in the formation of tumor
initiating cells (TICs), through a signaling pathway involving the RNA binding protein hnRNP E1 (E1). Herein,
our data demonstrates that this TGFβ/E1/ signaling pathway leads to the induction of an embryonic lncRNA
known as Platr18 (pluripotent associated transcript 18). We show that this lncRNA is not expressed in normal
epithelium or other adult somatic tissues but is highly induced by the TGFβ/E1 axis and in cells having
undergone an EMT or during cancer progression. The scientific premise of the proposal is that the TGFβ-
mediated EMT program induces the generation of TICs and tumor progression through TGFβ/E1 signaling and
reactivation of silenced Platr18. Its goals are to delineate the molecular mechanism(s) of Platr18 function and
determine its role in modulating T-cell mediated immunity through VSIG-3 & tumor innervation through
Sema4F.

## Key facts

- **NIH application ID:** 10756125
- **Project number:** 5R01CA154663-14
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Philip H Howe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $355,038
- **Award type:** 5
- **Project period:** 2011-08-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756125

## Citation

> US National Institutes of Health, RePORTER application 10756125, TGFbeta-regulated epithelial-mesenchymal transition (EMT) (5R01CA154663-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10756125. Licensed CC0.

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