Inhibition of Notch Signaling via IMR-1A In MBA-DB-231
Faculty Mentor
Jason Ashley
Presentation Type
Poster
Start Date
4-14-2026 2:00 PM
End Date
4-14-2026 4:00 PM
Location
PUB NCR
Primary Discipline of Presentation
Biology
Abstract
Triple-Negative Breast Cancer (TNBC) lacks ER, PR, and HER2 expression, limiting treatment options and contributing to high rates of recurrence and metastasis1. Because Notch signaling is frequently upregulated in TNBC, this study investigated IMR-1A, a selective inhibitor that blocks the formation of the Notch transcriptional activation complex by preventing MAML1 recruitment1,2. Using MDA-MB-231 TNBC cells, we assessed IMR-1A’s effects on viability, morphology, Notch pathway activity, migration, and 3D spheroid formation. IMR-1A caused dose-dependent morphological changes, including rounding and reduced adherence, but did not induce significant cell death or impair scratch-wound migration. Flow cytometry and qPCR both showed reduced HES1 protein and Hes1 mRNA levels, confirming partial inhibition of Notch-dependent transcription. SEM imaging further demonstrated structural disruption, with IMR-1A–treated cells displaying compact, rounded shapes and diminished surface protrusions. The strongest functional effect was observed in 3D culture where control cells formed numerous compact spheroids, while IMR-1A markedly reduced spheroid number and integrity, indicating impaired cell–cell organization and Notch-dependent coordination. Overall, IMR-1A alters cell structure and suppresses Notch signaling without causing cytotoxicity, suggesting its potential as an anti-metastatic rather than cytotoxic therapeutic candidate for TNBC. Further optimization and combinatorial studies are warranted.
Recommended Citation
Stepniak, Martyna and Mbabazi, Organ, "Inhibition of Notch Signaling via IMR-1A In MBA-DB-231" (2026). 2026 Symposium. 3.
https://dc.ewu.edu/srcw_2026/ps_2026/p3_2026/3
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Inhibition of Notch Signaling via IMR-1A In MBA-DB-231
PUB NCR
Triple-Negative Breast Cancer (TNBC) lacks ER, PR, and HER2 expression, limiting treatment options and contributing to high rates of recurrence and metastasis1. Because Notch signaling is frequently upregulated in TNBC, this study investigated IMR-1A, a selective inhibitor that blocks the formation of the Notch transcriptional activation complex by preventing MAML1 recruitment1,2. Using MDA-MB-231 TNBC cells, we assessed IMR-1A’s effects on viability, morphology, Notch pathway activity, migration, and 3D spheroid formation. IMR-1A caused dose-dependent morphological changes, including rounding and reduced adherence, but did not induce significant cell death or impair scratch-wound migration. Flow cytometry and qPCR both showed reduced HES1 protein and Hes1 mRNA levels, confirming partial inhibition of Notch-dependent transcription. SEM imaging further demonstrated structural disruption, with IMR-1A–treated cells displaying compact, rounded shapes and diminished surface protrusions. The strongest functional effect was observed in 3D culture where control cells formed numerous compact spheroids, while IMR-1A markedly reduced spheroid number and integrity, indicating impaired cell–cell organization and Notch-dependent coordination. Overall, IMR-1A alters cell structure and suppresses Notch signaling without causing cytotoxicity, suggesting its potential as an anti-metastatic rather than cytotoxic therapeutic candidate for TNBC. Further optimization and combinatorial studies are warranted.
