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Regulation of Human Tumorigensis by Cancer Specific NXF1 Adaptor Proteins

Award Number: R01CA269303
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Regulation of Human Tumorigensis by Cancer Specific NXF1 Adaptor Proteins - Project Summary/Abstract Background: Cancer originates from genetic alterations that lead to changes in gene expression programs that promote tumor survival, growth, motility and inhibits differentiation and apoptosis. The mRNAs from this oncogenic gene expression program must be exported to the cytoplasm to be translated into protein in order to promote tumorigenesis. Whether there is regulation of export of tumor specific mRNAs and the potential proteins involved in this process is unknown. We have shown that tumor specific NXF1 adaptor proteins regulate export of oncogenic mRNAs. The adaptor proteins are also highly upregulated during tumor initiation and knockdown of specific adaptors inhibit tumorigenesis. Objective/hypothesis: This proposal seeks to understand the molecular mechanisms driving the progression from normal to neoplastic skin using a RAS driven human epidermal tumor model. Our preliminary data suggests that 4 adaptor proteins are highly upregulated during tumor initiation that associates with NXF1 to mediate the export of the oncogenic gene expression program. Our objective is to characterize the role of each tumor induced NXF1 adaptor protein in the progression of normal to neoplastic skin. Furthermore we seek to determine the specific transcripts that each adaptor protein binds during tumor initiation to promote tumorigenesis. Specific Aims: (1) To determine the role of NXF1 adaptor proteins in the progression from normal to neoplastic skin and (2) to identify the transcripts associated with NXF1 adaptor proteins and determine which bound transcripts are exported. Study Design: To study epidermal tumorigenesis in a more clinically relevant setting, we generate 3-dimensionally intact human skin, containing human epidermal cells (that have been permanently knocked down for adaptor proteins) in the context of human dermal stroma and basement membrane, regenerated on immune compromised mice. By using this model, we can perform loss of function experiments on NXF1 adaptor proteins in regenerated human skin to characterize their role in epidermal growth, differentiation, and progression to neoplasia. We will use CLIP-Seq to determine the RNAs associated with each adaptor protein during the progression from normal to neoplastic epidermis.


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 = $361,425 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Biology Research	000	4	2/13/2025	NON-COMPETING CONTINUATION	$325,283
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Biology Research	001	4	5/22/2025	NON-COMPETING CONTINUATION	$36,142
														Subtotal = $361,425

Issue Date FY: 2024 ( Subtotal = $343,355 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Biology Research	000	3	4/16/2024	NON-COMPETING CONTINUATION	$343,355
														Subtotal = $343,355

Issue Date FY: 2023 ( Subtotal = $354,197 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Biology Research	000	2	3/24/2023	NON-COMPETING CONTINUATION	$354,197
														Subtotal = $354,197

Issue Date FY: 2022 ( Subtotal = $361,425 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Biology Research	000	1	3/23/2022	NEW	$361,425
														Subtotal = $361,425

Grand Total All Awards = $1,420,402

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Regulation of Human Tumorigensis by Cancer Specific NXF1 Adaptor Proteins

Award Number: R01CA269303

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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