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

Award Number: R16GM145484
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $145,106 )
2024	2024	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	3	4/30/2024	NON-COMPETING CONTINUATION	$145,106
														Subtotal = $145,106

Issue Date FY: 2023 ( Subtotal = $143,934 )
2023	2023	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	2	5/1/2023	NON-COMPETING CONTINUATION	$143,934
														Subtotal = $143,934

Issue Date FY: 2022 ( Subtotal = $142,652 )
2022	2022	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	1	5/25/2022	NEW	$142,652
														Subtotal = $142,652

Grand Total All Awards = $431,692

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

Award Number: R16GM145484

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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