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Investigating the Roles and Regulation of FOXO Transcription Factors in GBM and basal breast cancer

Award Number: SC3GM132053
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY: This proposal examines newly identified cellular roles for FOXO transcription factors in regulating stem cell- related gene expression and signal transduction in cancer. The phosphatidylinositol 3 kinase (PI3K) pathway is almost universally mutated to an activate state in cancer to drive growth and survival. Partially redundant, evolutionarily conserved FOXO -1, -3 and -4 transcription factors are best known for hindering cell cycle progression and inducing apoptosis on the PI3K pathway. Canonically, PI3K indirectly inactivates FOXO factors. However, we found FOXO factors in the nucleus of PI3K-activated cancer cell lines such as U87MGs and BT549s, suggesting novel regulation and roles for these factors in these settings. Other researchers have found FOXO factors in the nucleus in contexts with activated PI3K (embryonic stem cells and DLBCL). To address the role of FOXO factors in PI3K-activated cancers such as U87MG, we utilized an innovative approach (CRISPR, corroborated with RNAi and overexpression studies). Our preliminary evidence indicated that FOXO3 disruption reduced the expression of stem cell-related genes in U87MGs such as OCT4 and SOX2, whereas exogenous FOXO3 induced these genes. Aim 1 will identify mechanisms that promote FOXO nuclear localization in these novel contexts. Aim 2 will define precise molecular mechanisms that are utilized by FOXO factors to induce the expression of stem cell-related genes in PI3K-activated cancers such as U87MG and BT549 cells. These aims will be accomplished by employing qRT-PCR, western blot analyses, chromatin immuno-precipitation analyses, genomics approaches and confocal microscopy. The impact of FOXO factors on stem cell gene expression and signal transduction has broad ramifications to prevalent human diseases such as cancer, neurodegeneration, diabetes and aging. Proposed studies and research enhancement objectives will be conducted at the second largest Hispanic-serving Institution in the United States, the University of Texas Rio Grande Valley (UTRGV), which has not been a major recipient of NIH support. Funding and completion of these studies will increase research capabilities at UTRGV, which serves over 27,000 students who are 89% Hispanic thereby serving the mission of the SCORE Program.


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 = $0 )
2024	2022	THE UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	4	2/27/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $108,975 )
2022	2022	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	001	4	6/20/2022	NON-COMPETING CONTINUATION	$10,898
2022	2022	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	4	3/1/2022	NON-COMPETING CONTINUATION	$98,077
														Subtotal = $108,975

Issue Date FY: 2021 ( Subtotal = $108,975 )
2021	2021	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	3	2/24/2021	NON-COMPETING CONTINUATION	$108,975
														Subtotal = $108,975

Issue Date FY: 2020 ( Subtotal = $108,975 )
2020	2020	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	2	3/31/2020	NON-COMPETING CONTINUATION	$108,975
														Subtotal = $108,975

Issue Date FY: 2019 ( Subtotal = $108,975 )
2019	2019	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	2102 TREASURE HILLS BLVD STE 3.100	HARLINGEN	TX	78550	CAMERON	USA	Biomedical Research and Research Training	000	1	3/1/2019	NEW	$108,975
														Subtotal = $108,975

Grand Total All Awards = $435,900

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Investigating the Roles and Regulation of FOXO Transcription Factors in GBM and basal breast cancer

Award Number: SC3GM132053

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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