# Exploring oncogenic translation programs in cancer

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $426,103

## Abstract

Abstract
Our study explores mechanisms of translational control in leukemia and we will test new
methods of cancer detection and therapy. Specifically, the translation factors eIF4E (4E)
and eIF4A (4A) are highly expressed in human T-cell leukemia (T-ALL) specimens.
Moreover, both factors act as oncogenic drivers in a murine T-ALL model (Wendel et al.
2004, Wolfe et al. 2014). We want to understand how aberrant translation promotes
leukemia development and whether these changes provide opportunities for detection
and therapy. Our recent work has shed light on 4A's role in T-ALL (Wolfe et al. 2014):
For example, we found that 4A is needed to unwind RNA G-quadruplex (GQ) structures
that mark the 5'UTRs of T-ALL oncogenes such as MYC, NOTCH, MYB (Wolfe et al.
2014). Accordingly, selective inhibitors of 4A (e.g. silvestrol) show powerful activity in T-
ALL at dose levels that are tolerable in vivo. We will now focus on the translation
program driven by the oncogenic 4E factor and further test diagnostic and therapeutic
implications of aberrant mRNA translation in cancer. In principle, aberrant translation in
cancer may simply increase overall protein production. However, we speculate that
oncogenic translation factors like 4E and 4A drive specific translation programs that are
encoded in a transcript's regulatory elements. This hypothesis is based on our recent
identification of a conserved 4A responsive element in the 5'UTR of ~200 mRNAs in T-
ALL (Wolfe et al. 2014). In Aims 1 and 2 we propose a systematic analysis to define
exactly how 4E contributes to oncogenic translation. This is a long-standing interest in
the lab and remains an important question in the field. In Aim 3 we turn to the
`translational' aspects and explore how we can use aberrant translation to detect and
treat cancer.

## Key facts

- **NIH application ID:** 9986700
- **Project number:** 5R01CA207217-05
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Hans-Guido Wendel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $426,103
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986700

## Citation

> US National Institutes of Health, RePORTER application 9986700, Exploring oncogenic translation programs in cancer (5R01CA207217-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9986700. Licensed CC0.

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