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The Molecular function of ecto 5' nucleotidase in fusion-negative rhabdomyosarcoma

Award Number: F31CA271675
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 09/02/2024

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The Molecular function of ecto 5' nucleotidase in fusion-negative rhabdomyosarcoma - Project Summary/Abstract Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue sarcoma characterized by the lack of myogenic differentiation. RMS is divided in two molecular categories: fusion positive (FP-RMS) carrying a balanced chromosomal translocation generating an oncogenic Pax3-FOXO1 or Pax7-FOXO1 protein, and fusion negative (FN-RMS) that does not include the fusion event. Current treatments for FN-RMS remain poor and the long-term event-free survival rate for FN-RMS metastatic patients is below 30%. TWIST2 transcription factor represses myogenesis by inhibiting MyoD function and knockdown of TWIST2 in FN-RMS is shown to inhibit tumor cell growth and enhance myogenic differentiation. To understand the mechanisms underlying TWIST2 function in FN-RMS, we sought to identify its direct transcriptional targets. Among them, we identified NT5E, encoding an ecto 5’-nucleotidase, as a direct target gene of TWIST2. NT5E’s main role is to convert adenosine- monophosphate to adenosine in the purinergic signaling pathway. NT5E has been shown to promote cancer progression, invasion and metastasis in human melanoma and breast cancer. However, it’s possible role in FN- RMS has not been explored. In this proposal, we hypothesize that NT5E contributes to FN-RMS tumor formation and progression through the activation of the purinergic signaling pathway. To test this hypothesis, we will investigate the contribution of NT5E expression to the pathogenesis of FN-RMS in vitro and in vivo. Then, we will delineate the molecular mechanism whereby NT5E promotes FN-RMS. Completion of this research plan will push the boundaries of our knowledge regarding the role of NT5E in FN-RMS pathogenesis with the ultimate goal of developing novel therapeutic strategies for FN-RMS.


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 = -$37,469 )
2025	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	000	3	5/30/2025	NON-COMPETING CONTINUATION	-$21,113
2025	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	001	3	7/25/2025	NON-COMPETING CONTINUATION	-$16,356
														Subtotal = -$37,469

Issue Date FY: 2024 ( Subtotal = $38,389 )
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	000	3	5/7/2024	NON-COMPETING CONTINUATION	$38,389
														Subtotal = $38,389

Issue Date FY: 2023 ( Subtotal = $36,851 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	000	2	4/26/2023	NON-COMPETING CONTINUATION	$36,851
														Subtotal = $36,851

Issue Date FY: 2022 ( Subtotal = $35,664 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	002	1	8/15/2022	NEW	$716
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	001	1	4/22/2022	NEW	$0
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Research Manpower	000	1	4/22/2022	NEW	$34,948
														Subtotal = $35,664

Grand Total All Awards = $73,435

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The Molecular function of ecto 5' nucleotidase in fusion-negative rhabdomyosarcoma

Award Number: F31CA271675

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 09/02/2024

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