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A DUAL ROLE OF INTEGRIN ALPHA-3 IN BREAST CANCER CNS METASTASIS & CHEMORESISTANCE

Award Number: F31CA257758
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 05/12/2023

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A DUAL ROLE OF INTEGRIN ALPHA-3 IN BREAST CANCER CNS METASTASIS & CHEMORESISTANCE - ABSTRACT Integrins serve a multifaceted role in cancer progression by regulating cell migration as well as mediating signaling pathways important in proliferation and chemoresistance. Our lab was the first to demonstrate that leukemia cells use a neural stem cell migratory pathway to invade the central nervous system (CNS) by migrating along the abluminal surface of blood vessels that traverse the bone marrow and leptomeninges (LM). We showed that this process was mediated by leukemia cell integrin α6 engaging laminin in the basement membrane surrounding these vessels. Similar to leukemia, breast cancer metastasis to the LM results in severe morbidity and is a rapidly fatal complication. My preliminary data suggest that breast cancer cells utilize both α6 and α3 integrin-laminin interactions to invade the LM. I have also observed that breast cancer cells plated on laminin exhibit resistance to the chemotherapeutic doxorubicin. Integrin α6 KO does not sensitize the cells to chemotherapy leading me to hypothesize that integrin α3 serves a multifaceted role by activating chemoprotective signaling pathways upon laminin engagement. In this research grant, I propose to more fully define the role of α3 integrin-laminin interactions in regulating triple negative breast cancer LM metastasis along emissary vessels and in promoting chemoresistance in the metastatic microenvironment.


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 = -$948 )
2024	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cancer Research Manpower	000	2	3/22/2024	NON-COMPETING CONTINUATION	-$948
														Subtotal = -$948

Issue Date FY: 2023 ( Subtotal = -$3,542 )
2023	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cancer Research Manpower	000	2	9/6/2023	NON-COMPETING CONTINUATION	-$3,542
														Subtotal = -$3,542

Issue Date FY: 2022 ( Subtotal = $38,877 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	000	2	6/16/2022	NON-COMPETING CONTINUATION	$38,877
														Subtotal = $38,877

Issue Date FY: 2021 ( Subtotal = $38,161 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	001	1	6/22/2021	NEW	$0
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	000	1	6/22/2021	NEW	$38,161
														Subtotal = $38,161

Grand Total All Awards = $72,548

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A DUAL ROLE OF INTEGRIN ALPHA-3 IN BREAST CANCER CNS METASTASIS & CHEMORESISTANCE

Award Number: F31CA257758

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 05/12/2023

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