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EPHA2 Receptor Signaling in Breast Cancer Mechanotransduction

Award Number: R01CA262794
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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EPHA2 Receptor Signaling in Breast Cancer Mechanotransduction - SUMMARY Mechanical forces generated by a rigid extracellular matrix (ECM) in the tumor microenvironment play a key role in tumor progression and metastasis. We recently discovered a critical role of EPHA2 non-canonical signaling in promoting epithelial-mesenchymal transition (EMT) and tumor invasion and metastasis in response to increasing ECM stiffness in the tumor microenvironment. Furthermore, we found that activation of EPHA2 canonical signaling by the ephrinA1 ligand potently inhibits stiffness-induced breast cancer cell invasiveness. Based on these results, we hypothesize that EPHA2 functions as a key rheostat that integrates both mechanical and biochemical cues from the tumor microenvironment to regulate mechanosignaling in breast cancer progression and metastasis. We propose to combine biochemical, 2D and 3D cell culture assays, and in vivo xenograft models to elucidate EPHA2 signaling mechanisms in breast cancer malignancy induced by ECM rigidity through three specific aims. (1) Determine how ECM rigidity activates EPHA2 non-canonical signaling to promote EMT and invasion. (2) Determine how EPHA2 canonical signaling blocks EMT and invasion induced by ECM rigidity. (3) Examine the role of EPHA2 non-canonical and canonical signaling in breast cancer invasion and metastasis in vivo. Together, these studies will inform on the potential usefulness of activating EphA2 canonical signaling for inhibition of breast cancer invasiveness and metastasis.


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 = $535,039 )
2025	2025	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	000	4	6/2/2025	NON-COMPETING CONTINUATION	$535,039
														Subtotal = $535,039

Issue Date FY: 2024 ( Subtotal = $620,121 )
2024	2024	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	001	3	9/10/2024	SUPPLEMENT FOR EXPANSION	$111,834
2024	2024	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	000	3	5/10/2024	NON-COMPETING CONTINUATION	$508,287
														Subtotal = $620,121

Issue Date FY: 2023 ( Subtotal = $520,482 )
2023	2023	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	000	2	6/7/2023	NON-COMPETING CONTINUATION	$520,482
														Subtotal = $520,482

Issue Date FY: 2022 ( Subtotal = $551,618 )
2022	2022	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	000	1	4/14/2022	NEW	$551,618
														Subtotal = $551,618

Grand Total All Awards = $2,227,260

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EPHA2 Receptor Signaling in Breast Cancer Mechanotransduction

Award Number: R01CA262794

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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