# TGF beta - Regulated EMT

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $355,063

## Abstract

Abstract
The epithelial-mesenchymal transition (EMT), in which cells undergo a switch from a polarized, epithelial
phenotype to a highly motile fibroblastic or mesenchymal phenotype is fundamental during embryonic
development and can be reactivated in a variety of diseases including fibrosis and cancer. In addition to
generating cells with increased migratory and invasive potential, recent data suggests that EMT represents a
program that leads to the formation of both normal and neoplastic mammary epithelial stem cells, the latter
representing cells that exhibit cancer stem cells (CSC)-like properties. Epithelial cells in the normal mammary
gland, and by extension in other epithelial organs, employ components of the EMT program as the main route
for entering into the stem cell (SC) state. We have identified a transcript-selective translational regulatory
pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear
ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3'-UTR
regulatory BAT (TGFβ activated translation) element and silences translation of mRNAs that mediate EMT.
TGFβ activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific
stimulation of protein kinase Bβ/Akt2, inducing the release of the mRNP complex from the 3'-UTR element,
resulting in the reversal of translational silencing and increased expression of EMT-inducer mRNAs. Two of
these mRNAs, the kinase Jak2 and a cytokine termed interleukin-like EMT-inducer (ILEI), and how they
regulate TGFβ-induced EMT and induction of mammary stem cells (MaSCs) are the focus of the current
application. We hypothesize that the TGFβ-induced EMT program mediates generation of MaSCs through
hnRNP E1-regulated translational control of ILEI and Jak2. ILEI functions in an autocrine manner to mediate
Jak2/Stat3-dependent and -independent signaling required for the EMT and generation of MaSCs. Thus, the
goal of this proposal is to delineate the ILEI signaling pathway and to determine its functional significance in
mediating MaSC formation.

## Key facts

- **NIH application ID:** 10070575
- **Project number:** 5R01CA154663-11
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Philip H Howe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,063
- **Award type:** 5
- **Project period:** 2011-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070575

## Citation

> US National Institutes of Health, RePORTER application 10070575, TGF beta - Regulated EMT (5R01CA154663-11). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10070575. Licensed CC0.

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