Targeting the TRIM29-focal adhesion axis to block bladder cancer muscle invasion

Active Project Grant Awarded Last action

Award ID
F31CA301566
Recipient
Awarding agency
Obligated
$94,316

Award facts

Assistance listing
93.398 Cancer Research Manpower
Completion date 0% complete
Originally
Place of performance
Ann Arbor, MI 48109, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Bladder cancer is the sixth most common cancer in the U.S., with an estimated ~85,000 new diagnoses and >17,000 deaths in 2025. The most crucial determinant of patient survival is the degree of tumor invasion into the surrounding muscle wall. While non-muscle invasive tumors are common and readily treatable with excellent survival rates, muscle invasive tumors frequently metastasize despite aggressive therapy and 50% of these patients succumb to the disease. Therefore, there is an urgent need to characterize molecular mechanisms of invasive progression and therapeutically target these processes. As such, we have previously identified the TRIM29 gene as a critical driver of bladder cancer invasive progression. TRIM29 promotes invasive progression by regulating cellular migration through focal adhesions (FA) and increased FAK/SRC signaling. Focal adhesions are cytoplasmic complexes that receive integrin-mediated signals from the extracellular environment to coordinate cellular migratory responses. The mechanism by which TRIM29 regulates FA stability and signaling to promote invasion is unclear. Paxillin (PXN) is a critical subunit of FA complexes that regulates FA stability and coordinates downstream FAK/SRC signaling. Our preliminary data suggests that TRIM29 interacts with PXN, via an inducible phosphorylation event on TRIM29 S550, to regulate FA biology. The central hypothesis of this proposal is that TRIM29'S phosphorylated S550 residue promotes bladder cancer invasion by binding PXN, which stabilizes focal adhesions and mediates increased FAK/SRC signaling, and that targeting PTRIM29 S550/FAK/SRC will block invasive progression. This hypothesis will be tested through two specific aims: 1) to characterize the mechanism by which TRIM29 regulates FAK/SRC signaling in bladder cancer migration and invasion. 2) to determine the optimal therapeutic strategy to block TRIM29-mediated invasive progression utilizing compounds targeting PTRIM29 S550, FAK and SRC. Aim 1 will utilize molecular biology and advanced live cell microscopy techniques to assess the critical domains of TRIM29 and PXN that mediate FA stability, increased FAK/SRC signaling, and cell migration/invasion. In vitro findings will be confirmed in mouse and human tumor models. Aim 2 will leverage patient-derived organoids and in vivo models to evaluate novel and established small molecules for reduction of tumor invasion. Successful completion of this proposal will define the novel mechanism of TRIM29-mediated invasive progression and will identify treatments to specifically block progression of high-risk, non-muscle invasive, TRIM29+ tumors to the lethal invasive disease. Lastly, this fellowship will develop my expertise in pharmacology, pathology, microscopy, bioinformatics, and academic leadership. The rich training environment, plentiful core resources, and my diverse and experienced mentorship team at the university of michigan will facilitate my fruitful completion of these aims and my training toward becoming an independent researcher in translational oncology.

Transactions

Action Obligated Date
Amendment $47,158
Amendment $47,158
Original award $0

Quick answers

Who received award F31CA301566?

F31CA301566 was awarded to Regents Of The University Of Michigan by National Cancer Institute (National Institutes of Health) on December 10, 2026.

How much is award F31CA301566 worth?

$94,316 has been obligated on F31CA301566.

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