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Mitochondrial lateral transfer during metastasis

Award Number: R37CA247994
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2028
AWARD TERMINATION DATE: 04/25/2025

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Mitochondrial lateral transfer during metastasis - Project Summary Macrophages play paradoxical roles in cancer: They can be tumoricidal, but in many cancers, macrophages promote metastasis. There has been growing evidence that macrophages can modulate cell behavior via unconventional cell contact-mediated communication in development and homeostasis. We have recently extended these paradigms by discovering that macrophages laterally transfer mitochondria to breast cancer cells, promoting cancer cell proliferation. Mitochondria are dynamic organelles that perform a variety of essential cellular functions. Mitochondria have been shown to transfer to tumor cells in vivo, restoring their respiration and ability to form tumors. While these elegant “proof of principle” studies demonstrated that mitochondrial lateral transfer can occur in the tumor microenvironment, it was unclear how a relatively small population of exogenous mitochondria changes the behavior of the recipient cancer cell, particularly if the recipient cancer cell already has a functional endogenous mitochondrial network. In now recently published work, we found that transferred macrophage mitochondria are dysfunctional and accumulate reactive oxygen species. Accumulated reactive oxygen species at transferred mitochondria then promotes breast cancer cell proliferation in an ERK-dependent manner. These results suggest that transferred mitochondria do not promote cancer cell proliferation via restoration of bioenergetics. Rather, transferred mitochondria act as a signaling source, promoting cancer cell behaviors. These unexpected findings led us to ask whether this form of communication is specific to macrophages and cancer cells, or whether mitochondrial transfer between other cells in the tumor environment use this process to regulate proliferation. This question forms the basis of the extension period of the R37 award. Our preliminary results suggest that mitochondrial transfer between cancer cells may use different strategies, and thus, in updated aim 1, we propose to determine the mechanism by which mitochondrial transfer between cancer cells promotes cancer cell proliferation. We will also determine whether mitochondrial transfer from highly metastatic cancer cells promote metastatic behaviors of recipient weakly metastatic cells in vitro and in vivo. Furthermore, in updated aim 2, we have excitingly built a new tool to detect mitochondrial transfer with higher sensitivity, allowing us to delve into new mechanisms underlying mitochondrial transfer. Taken together, these experiments will reveal how mitochondrial transfer instructs breast cancer cells to become more robust and metastatic. Our goals are to define how immune cells function in the tumor microenvironment, and to provide a basis for developing future immunotherapies that limit 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: 2026 ( Subtotal = $317,048 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	000	6	2/2/2026	EXTENSION WITH OR WITHOUT FUNDS	$317,048
														Subtotal = $317,048

Issue Date FY: 2025 ( Subtotal = $348,844 )
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	001	5	3/21/2025	NON-COMPETING CONTINUATION	$313,959
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	003	5	4/25/2025	NON-COMPETING CONTINUATION	$0
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	004	5	5/22/2025	NON-COMPETING CONTINUATION	$34,885
2025	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	000	4	1/15/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	002	4	4/24/2025	TERMINATION	$0
														Subtotal = $348,844

Issue Date FY: 2024 ( Subtotal = $693,329 )
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	002	4	8/22/2024	SUPPLEMENT FOR EXPANSION	$44,879
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	000	4	1/19/2024	NON-COMPETING CONTINUATION	$313,959
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	003	4	9/12/2024	SUPPLEMENT FOR EXPANSION	$317,048
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	001	4	4/16/2024	NON-COMPETING CONTINUATION	$17,443
														Subtotal = $693,329

Issue Date FY: 2023 ( Subtotal = $341,867 )
2023	2023	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	000	3	7/20/2023	NON-COMPETING CONTINUATION	$341,867
														Subtotal = $341,867

Issue Date FY: 2022 ( Subtotal = $348,844 )
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	001	2	5/23/2022	NON-COMPETING CONTINUATION	$34,885
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	000	2	1/31/2022	NON-COMPETING CONTINUATION	$313,959
														Subtotal = $348,844

Issue Date FY: 2021 ( Subtotal = $348,844 )
2021	2021	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Cancer Biology Research	000	1	12/16/2020	NEW	$348,844
														Subtotal = $348,844

Grand Total All Awards = $2,398,776

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Mitochondrial lateral transfer during metastasis

Award Number: R37CA247994

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2028

AWARD TERMINATION DATE: 04/25/2025

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