Thursday, December 4, 2025 12/4/2025

Elucidating the Relationship Between Cell Proliferation and Invasion

Award Number: F30CA257383
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 05/19/2025

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Elucidating the Relationship Between Cell Proliferation and Invasion - PROJECT SUMMARY/ABSTRACT Over the last five years, three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have been approved for the treatment of metastatic breast cancer. CDK4/6i prevent cancer cells from dividing by blocking their progression through the G1/G0 phase of the cell cycle. However, results from in vitro studies reveal that both exogenous and endogenous CDK4/6i increase the invasiveness of certain forms of cancer. The consequences of G1/G0 cell cycle arrest on cancer cell behavior in vivo remain unknown. Caenorhabditis elegans anchor cell (AC) invasion provides an excellent yet simple in vivo model of cell invasive behavior that allows single-cell and subcellular analysis of cell invasion through basement membrane. Our lab determined that G1/G0-specific arrest is required for AC invasion to occur and that the nuclear hormone receptor NHR-67/TLX acts as a key regulator of this process. In the absence of NHR-67, the AC becomes non-invasive but over-proliferates, indicating that proliferation can increase as invasion is blocked. The long-term goal is to understand both the molecular mechanisms controlling G1/G0 cell cycle arrest and the in vivo effects of CDK4/6i as individual agents and in combination with inhibitors of the mammalian target of rapamycin (mTORi). Together, CDK4/6i and mTORi have been shown to induce senescence in cancer cells in vitro, suggesting that combining these pharmacological agents might be useful in the clinical setting. The overall objectives of this fellowship application are to (i) elucidate how G1/G0 is maintained in the C. elegans AC and (ii) determine whether ACs in NHR-67-deficient animals can be pharmacologically induced to transition from proliferation-to-invasion-to-senescence. Based on preliminary data and prior research, the central hypothesis is that redundant mechanisms regulate the G1/G0 state of the wild-type AC and that proliferative ACs in NHR-67-deficient animals can be prompted to undergo senescence. This central hypothesis will be tested by pursuing two specifics aims. Aim 1 will identify the components regulating G1/G0 arrest in the pro-invasive AC. Aim 2 will evaluate the transition between AC proliferation, invasion and senescence upon depletion of CDK4/6, mTOR, or both. To address these aims, this project will use established gene knockdown techniques, high-resolution imaging, and cutting-edge technologies, including a novel live cell cycle state sensor and two conditional protein depletion systems. The results of these studies can help guide the development of future treatment strategies for aggressive cancers.


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 = -$5,614 )
2026	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	4	11/21/2025	NON-COMPETING CONTINUATION	-$5,614
														Subtotal = -$5,614

Issue Date FY: 2024 ( Subtotal = $53,974 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	4	7/1/2024	NON-COMPETING CONTINUATION	$53,974
														Subtotal = $53,974

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	3	7/14/2023	NON-COMPETING CONTINUATION	$52,694
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $38,965 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	2	6/24/2022	NON-COMPETING CONTINUATION	$38,965
														Subtotal = $38,965

Issue Date FY: 2021 ( Subtotal = $38,249 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	002	1	2/24/2021	NEW	$0
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	1	2/19/2021	NEW	$35,528
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	001	1	2/24/2021	NEW	$2,721
														Subtotal = $38,249

Grand Total All Awards = $178,268

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Elucidating the Relationship Between Cell Proliferation and Invasion

Award Number: F30CA257383

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 05/19/2025

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