# Translational control of EMT by the CELF1 RNA Binding Protein

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $80,000

## Abstract

By some estimates, tumor metastasis is responsible for over 90% of cancer mortality. At the cellular
level, epithelial to mesenchymal transition (EMT) is the initiating event in tumor metastasis. We have
been investigating the contribution of translational control to TGF-β-induced EMT in a breast epithelial
model. Our preliminary data unambiguously demonstrate that the CELF1 RNA binding protein, most
well known for its role in Type 1 Myotonic Dystrophy, is both necessary and sufficient for EMT in this
system. In epithelial cells, the CELF1 protein is actively degraded via the proteasome. However, upon
TGF-β addition and EMT, this protein is stabilized and appears to increase the translation of several
target genes, some of which have already been defined as positive regulators of EMT. To our
knowledge this is the first data directly demonstrating the role of this gene product in EMT.
Our overall objective is to further elucidate the mechanism by which TGF-β induces EMT via the
CELF1 protein. We predict that a more developed understanding of the cellular mechanisms at play in
this pathway will reveal enzymatic activities playing critical roles in EMT, and that eventual therapeutic
targeting of these activities may be viable therapeutic targets for the prevention of metastasis in early
stage cancers. We hope to achieve our objective by testing our core hypothesis that induced stability
of CELF1 protein drives EMT via translational activation of distinct downstream effector proteins. We
propose doing this via three Specific Aims. First, we will identify the downstream effectors by which
CELF1 promotes EMT and tumor metastasis in experimental models via a candidate approach. Using
classical biochemical approaches, we will next establish the mechanism by which TGF-β treatment
leads to an increase in CELF1 protein levels. Finally, we will determine to what extent misexpression of
CELF1 impacts tumor colonization and metastasis in in vivo models, and survey a broad range of
human breast cancers to determine whether CELF1 is misexpressed in these tumors as compared to
normal tissue.
The proposed work is directly relevant to cancer because EMT is a core mechanism underlying tumor
metastasis. Identification of the enzymatic activities by which CELF1 stability and function are
controlled in the context of EMT will reveal candidate therapeutic targets for the prevention of
metastasis of early-stage cancers. Downstream effectors of the CELF1 protein may also prove to be
potential therapeutic targets, but are certain to provide insight into the cellular mechanisms underlying
EMT that may be translatable to a broad range of solid tumors.

## Key facts

- **NIH application ID:** 10395222
- **Project number:** 3R01CA190467-05S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Joel R Neilson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $80,000
- **Award type:** 3
- **Project period:** 2021-04-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395222

## Citation

> US National Institutes of Health, RePORTER application 10395222, Translational control of EMT by the CELF1 RNA Binding Protein (3R01CA190467-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10395222. Licensed CC0.

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