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Oncogenic Impact of eIF4E-dependent RNA Export in Cancer

Award Number: R01CA080728
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/1999
PERIOD OF PERFORMANCE END DATE: 02/28/2028

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Oncogenic Impact of eIF4E-dependent RNA Export in Cancer - Abstract This renewal application investigates the impact of dysregulated RNA processing in cancer. Dysregulation of these events can elevate the production of proteins that function in all facets of malignancy, without altering their transcript levels. The eukaryotic translation initiation factor eIF4E, dysregulated in many cancers including in acute myeloid leukemia (AML), governs the RNA processing of networks of transcripts that ultimately underpin its oncogenic activities. Its ability to govern these regulons has been attributed to its well-established roles in nuclear export and translation of specific RNAs. eIF4E elevation in cancer patients is correlated with aggressive disease and poor outcomes. Here, we discovered that eIF4E reprograms various facets of cell motility including adherence, migration, and invasion through its effects on RNA processing. Indeed, we identified eIF4E-dependent RNA export targets that encode factors which are key modulators of cell motility including hyaluronan, its main receptor CD44 and ezrin. Ezrin is an intracellular protein that links CD44 signalling to cytoskeletal changes that alter adherence, migration, and invasion. Furthermore, eIF4E directly interacts with ezrin. Three aims are proposed to dissect the mechanistic principles and biological impacts related to these novel findings. We will uncover the requirements for eIF4E to drive cell movement, determine the role of the ezrin- eIF4E complex in translation and motility, and examine the role of the HA/CD44/ezrin axis in eIF4E-dependent AML cell motility in mouse models. Our studies provide a unique opportunity to identify novel biochemical mechanisms that underpin aggressive disease associated with dysregulated eIF4E.


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: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITE DE MONTREAL	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC			CAN	Cancer Biology Research	000	22	3/7/2025	NON-COMPETING CONTINUATION	-$69,042
2025	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	001	23	3/7/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$69,042
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $245,894 )
2024	2024	UNIVERSITE DE MONTREAL	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC			CAN	Cancer Biology Research	000	22	1/25/2024	NON-COMPETING CONTINUATION	$232,952
2024	2024	UNIVERSITE DE MONTREAL	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC			CAN	Cancer Biology Research	001	22	4/17/2024	NON-COMPETING CONTINUATION	$12,942
														Subtotal = $245,894

Issue Date FY: 2023 ( Subtotal = $258,837 )
2023	2023	UNIVERSITE DE MONTREAL	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC			CAN	Cancer Biology Research	000	21	2/15/2023	COMPETING CONTINUATION	$258,837
														Subtotal = $258,837

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITE DE MONTREAL	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC			CAN	Cancer Biology Research	000	20	6/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $210,799 )
2020	2020	UNIVERSITE DE MONTREAL, L'	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC	H3T 1J4		CAN	Cancer Biology Research	000	20	2/19/2020	NON-COMPETING CONTINUATION	$210,799
														Subtotal = $210,799

Issue Date FY: 2019 ( Subtotal = $204,475 )
2019	2019	UNIVERSITE DE MONTREAL, L'	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC	H3T 1J4		CAN	Cancer Biology Research	000	19	2/6/2019	NON-COMPETING CONTINUATION	$204,475
														Subtotal = $204,475

Issue Date FY: 2018 ( Subtotal = $210,799 )
2018	2018	UNIVERSITE DE MONTREAL, L'	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC	H3T 1J4		CAN	Cancer Biology Research	001	18	5/22/2018	NON-COMPETING CONTINUATION	$21,080
2018	2018	UNIVERSITE DE MONTREAL, L'	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC	H3T 1J4		CAN	Cancer Biology Research	000	18	2/5/2018	NON-COMPETING CONTINUATION	$189,719
														Subtotal = $210,799

Issue Date FY: 2017 ( Subtotal = $210,799 )
2017	2017	UNIVERSITE DE MONTREAL, L'	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC	H3T 1J4		CAN	Cancer Biology Research	000	17	2/17/2017	NON-COMPETING CONTINUATION	$174,196
2017	2017	UNIVERSITE DE MONTREAL, L'	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC	H3T 1J4		CAN	Cancer Biology Research	001	17	3/17/2017	NON-COMPETING CONTINUATION	$15,523
2017	2017	UNIVERSITE DE MONTREAL, L'	2900 BOUL EDOUARD-MONTPETIT	MONTREAL	QC	H3T 1J4		CAN	Cancer Biology Research	002	17	6/7/2017	NON-COMPETING CONTINUATION	$21,080
														Subtotal = $210,799

Issue Date FY: 2016 ( Subtotal = $210,799 )
2016	2016	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	002	16	12/22/2015	COMPETING CONTINUATION	$210,799
2016	2014	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC		00000		CAN	Cancer Biology Research	000	15	12/17/2015	NON-COMPETING CONTINUATION	$0
2016	2014	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC		00000		CAN	Cancer Biology Research	001	15	12/18/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $210,799

Issue Date FY: 2014 ( Subtotal = $189,801 )
2014	2014	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	000	15	2/28/2014	NON-COMPETING CONTINUATION	$176,104
2014	2014	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	001	15	4/21/2014	NON-COMPETING CONTINUATION	$13,697
														Subtotal = $189,801

Issue Date FY: 2013 ( Subtotal = $183,929 )
2013	2013	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	000	14	2/5/2013	EXTENSION WITH OR WITHOUT FUNDS	$88,052
2013	2013	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	001	14	6/20/2013	EXTENSION WITH OR WITHOUT FUNDS	$95,877
														Subtotal = $183,929

Issue Date FY: 2012 ( Subtotal = $195,671 )
2012	2012	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	000	13	4/3/2012	NON-COMPETING CONTINUATION	$195,671
														Subtotal = $195,671

Issue Date FY: 2011 ( Subtotal = $195,673 )
2011	2011	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	001	12	5/13/2011	NON-COMPETING CONTINUATION	$8,674
2011	2011	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	000	12	1/28/2011	NON-COMPETING CONTINUATION	$186,999
														Subtotal = $195,673

Issue Date FY: 2010 ( Subtotal = $201,722 )
2010	2010	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	000	11	3/30/2010	COMPETING CONTINUATION	$201,722
														Subtotal = $201,722

Issue Date FY: 2009 ( Subtotal = $195,847 )
2009	2009	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC				CAN	Cancer Biology Research	000	10	3/30/2009	NON-COMPETING CONTINUATION	$195,847
														Subtotal = $195,847

Issue Date FY: 2007 ( Subtotal = $195,847 )
2007	2007	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC		00000		CAN	Cancer Biology Research	000	8	3/30/2007	NON-COMPETING CONTINUATION	$195,847
														Subtotal = $195,847

Issue Date FY: 2006 ( Subtotal = $201,696 )
2006	2006	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC		00000		CAN	Cancer Biology Research	000	7	4/18/2006	NON-COMPETING CONTINUATION	$201,696
														Subtotal = $201,696

Issue Date FY: 2005 ( Subtotal = $206,550 )
2005	2005	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC		00000		CAN	Cancer Biology Research	000	6	6/14/2005	COMPETING CONTINUATION	$206,550
														Subtotal = $206,550

Issue Date FY: 2003 ( Subtotal = $286,011 )
2003	2003	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Cancer Biology Research	000	5		NON-COMPETING CONTINUATION	$286,011
														Subtotal = $286,011

Issue Date FY: 2002 ( Subtotal = $277,683 )
2002	2002	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Cancer Biology Research	000	4	1/14/2002	NON-COMPETING CONTINUATION	$277,683
														Subtotal = $277,683

Grand Total All Awards = $4,635,415

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Oncogenic Impact of eIF4E-dependent RNA Export in Cancer

Award Number: R01CA080728

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/1999

PERIOD OF PERFORMANCE END DATE: 02/28/2028

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