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The non-canonical Collagen I-DDR1 signaling regulating protein synthesis during metastasis

Award Number: F31CA278582
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/22/2023
PERIOD OF PERFORMANCE END DATE: 12/21/2026

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The non-canonical Collagen I-DDR1 signaling regulating protein synthesis during metastasis - PROJECT SUMMARY The activation of signaling tumor cells via the tumor micrenvironment (TME) to undergo metastasis in bladder cancer is understudied. Clinically, increased Col I deposition correlates with bladder cancer progression (i.e. increasing tumor stage). Our published study demonstrated that Col I induces bladder tumor cells to invade and colonize the lung through Discoidin Domain Receptor 1 (DDR1) pathway. Yet, increase Col deposition is known to cause nutrient deprivation which is unsustainable for tumor growth. Tumors can adapt to these increasingly harsh environment by downregulating protein synthesis – a metabolically expensive homeostatic process. Interestingly, this downregulation of protein synthesis has also been shown to promote resistance to anoikis, cell death resulting from extracellular matrix detachment, which cancer cells must overcome when they undergo metastasis. To our knowledge, whether collagen outside-in signaling senses nutrient deprivation and thereafter reduces energy expenditure by attentuating protein synthesis has yet to be investigated. Interestingly, my pilot studies show two independent, yet complementary non-canonical mechanisms of downregulating protein synthesis, which involves Col I-DDR1 interaction. I now propose to 1) interrogate these two mechanisms that downregulate protein synthesis and 2) how this Col I-DDR1 mediated downregulation of protein synthesis affects the efficiency of cancer metastasis. Knowledge gained from the success of this proposal will yield newer insights on Col I-DDR1 interaction in promoting cancer cell survival and metastasis in bladder cancer.


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 = $43,138 )
2025	2025	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	000	2	11/19/2024	NON-COMPETING CONTINUATION	$41,294
2025	2025	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	001	2	2/13/2025	NON-COMPETING CONTINUATION	$0
2025	2025	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	002	2	8/21/2025	NON-COMPETING CONTINUATION	$1,844
														Subtotal = $43,138

Issue Date FY: 2023 ( Subtotal = $41,294 )
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	000	1	6/23/2023	NEW	$41,294
														Subtotal = $41,294

Grand Total All Awards = $84,432

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The non-canonical Collagen I-DDR1 signaling regulating protein synthesis during metastasis

Award Number: F31CA278582

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/22/2023

PERIOD OF PERFORMANCE END DATE: 12/21/2026

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