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Defining the role of PIM kinases in hypoxia-induced prostate cancer invasion

Award Number: F31CA254256
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/29/2022
PERIOD OF PERFORMANCE END DATE: 01/30/2023

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Defining the role of PIM kinases in hypoxia-induced prostate cancer invasion - PROJECT SUMMARY The prevention of invasion and metastasis remains paramount for the reduction of prostate cancer mortality. Locally confined tumors are rarely lethal and survival is all but assured until metastasis occur, thus understanding the mechanisms driving invasion are critical. Once possible driver is hypoxia, or low oxygenation. We do not know the biological mechanisms by which hypoxia drives metastasis and currently have no effective therapeutic options to prevent it. However, in this research proposal, we have reason to believe that hypoxia-induced PIM is leading to increased invasion and metastasis through regulation of Abi2 and actin polymerization. To test this hypothesis, we will determine how hypoxia modulates Abi2 levels and WRC formation. To do this we will investigate the effects of hypoxia-induced PIM phosphorylation on Abi2, determine effects of hypoxia and PIM on the WRC, and characterize the effect of hypoxia on actin dynamics. Additionally, we will investigate the role of PIM in hypoxia-induced invasion. The goal is to determine whether hypoxia-induced PIM is sufficient to drive invasion in vitro and understand the role of PIM in determining invasive potential of cells in vivo. These data should help in establishing a novel connection between PIM kinases and regulation of cell motility via cytoskeletal rearrangement in hypoxia. Elucidating mechanisms regulating motility and invasion are critical for understanding metastatic disease progression. In doing this project, we will establish a novel prostate-specific invasion model to better recapitulate what occurs in human disease. This will allow for better clarity into the metastatic process and ultimately should provide insight into how to improve overall patient survival. These results will elucidate the potential therapeutic role for PIM inhibitors and how they could be used to increase the efficacy of patient treatment. Lastly these data will also yield insight into mechanisms of how hypoxia increases invasion that could be exploited in the clinic and make a direct impact on patients care. In summary, the research proposed in the grant will elucidate mechanisms by which hypoxia is a driving factor in metastasis and provide insight into pathways that serve as viable drug targets to improve efficacy of patient treatment while simultaneously increasing overall patient survival.


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 = -$3,663 )
2024	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Research Manpower	001	2	12/28/2023	NON-COMPETING CONTINUATION	-$1
2024	2021	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Research Manpower	000	1	12/28/2023	NEW	-$3,662
														Subtotal = -$3,663

Issue Date FY: 2023 ( Subtotal = $1 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Research Manpower	001	2	3/24/2023	NON-COMPETING CONTINUATION	-$46,751
2023	2023	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Research Manpower	000	2	1/12/2023	NON-COMPETING CONTINUATION	$46,752
														Subtotal = $1

Issue Date FY: 2021 ( Subtotal = $46,036 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Research Manpower	000	1	7/23/2021	NEW	$46,036
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Research Manpower	001	1	7/23/2021	NEW	$0
														Subtotal = $46,036

Grand Total All Awards = $42,374

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Defining the role of PIM kinases in hypoxia-induced prostate cancer invasion

Award Number: F31CA254256

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/29/2022

PERIOD OF PERFORMANCE END DATE: 01/30/2023

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