# Role of the transcriptional corepressor TLE1 in the lung adenocarcinoma aggressiveness and progression

> **NIH NIH R16** · XAVIER UNIVERSITY OF LOUISIANA · 2022 · $142,652

## Abstract

Principal Investigator/Program Director (Last, first, middle): Biliran Jr., Hector
Role of the transcriptional corepressor TLE1 in the lung adenocarcinoma aggressiveness and
progression
Abstract
Lung adenocarcinoma (LUAD), which accounts for almost 40% of lung cancer, has a 5-year survival rate of
only 15% due to its aggressive behavior. Hence, there is an urgent need to better understand the molecular
events underlying the development and progression of LUAD. This lab's prior R15 work has obtained evidence
that the transcriptional corepressor TLE1 exerts an anti-apoptotic- and EMT-promoting function in LUAD cells
and thereby potentiating their anoikis resistance, and anchorage-independent growth in vitro as well as
tumorigenesis in vivo. Mechanistically, the dual survival- and EMT-promoting function of TLE1 is in part due to
its transcriptional silencing of the tumor suppressor E-cadherin gene via the transcription factor Zeb1 and
chromatin modifying enzyme Histone deacetylase (HDAC). Our recent bioinformatics analyses indicate that
TLE1 is upregulated and displays a poor prognostic value in LUAD. Based on these collective data, we
hypothesize that TLE1 regulates a survival- and EMT-promoting gene transcription program to drive the
aggressiveness and progression of LUAD. To test this hypothesis, the following specific aims will be
addressed: 1) Evaluate the functional role of TLE1 in LUAD tumorigenesis and aggressiveness; 2) Molecularly
characterize the components of the TLE1-mediated transcriptional program that may drive LUAD progression;
and 3) Determine whether TLE1 nuclear function regulates tumorigenicity and metastasis in LUAD mouse
xenograft models. These proposed studies, which will be performed by undergraduate research students
together with the PI and a Research Assistant, will advance our understanding of the TLE1 transcriptional
network as a “driver” of LUAD oncogenesis and as a molecular therapeutic target to curtail LUAD
aggressiveness.
PHS398 (Rev. 5/01) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10409913
- **Project number:** 1R16GM145484-01
- **Recipient organization:** XAVIER UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Hector Ramos Biliran
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $142,652
- **Award type:** 1
- **Project period:** 2022-06-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409913

## Citation

> US National Institutes of Health, RePORTER application 10409913, Role of the transcriptional corepressor TLE1 in the lung adenocarcinoma aggressiveness and progression (1R16GM145484-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10409913. Licensed CC0.

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