Description
- Abstract:
- Abstract of PIM1 Kinase as a Regulator of Aggressive Phenotypes in Cancer: Effects of Pharmacological Inhibition on Cell Survival and the Tumor Microenvironment, by Elizabeth A. Carrara, ScM, Brown University, May, 2026. Cancer progression is driven by mechanisms that promote cell survival, invasion, and interaction with the tumor microenvironment. The serine/threonine kinase PIM1 has been implicated in these processes; however, its role in aggressive solid tumors such as triple-negative breast cancer (TNBC) and glioblastoma (GBM) remains incompletely understood. This study aimed to evaluate the role of PIM1 in epithelial–mesenchymal transition (EMT), tumor cell survival, migration, and tumor–immune interactions in these cancer models. To address this, a combination of bioinformatic analyses and experimental approaches was employed. Publicly available datasets were analyzed to assess PIM1 expression, survival outcomes, and co-expression with key oncogenic markers. In vitro experiments were conducted using TNBC and GBM cell lines treated with PIM1 inhibitors (SGI1776 and TP3654). Cell viability was assessed using MTT assays, migration was evaluated through wound healing assays, and protein expression and signaling changes were analyzed by western blotting. Co-culture systems with T-lymphocytes were used to examine tumor–immune interactions. Bioinformatic results showed no significant association between PIM1 expression and survival or oncogenic markers in TNBC. In contrast, GBM exhibited elevated PIM1 expression and a significant association with poorer patient survival. Experimentally, PIM1 inhibition reduced cell viability and migration in GBM models and decreased activation of pro-survival signaling pathways. In TNBC, PIM1 expression decreased following EMT induction, suggesting a context-dependent role. Co-culture experiments revealed that PIM1 inhibition altered tumor–immune cell interactions, leading to increased cellular aggregation and changes in cellular organization. In conclusion, PIM1 plays a context-dependent role in cancer progression, with a more prominent functional significance in GBM than in TNBC. These findings support the potential of PIM1 as a therapeutic target in GBM and highlight its role in both tumor-intrinsic signaling and tumor microenvironment dynamics.
- Notes:
- Thesis (Sc. M.)--Brown University, 2026
Citation
Carrara, Elizabeth Agnello,
"PIM1 Kinase as a Regulator of Aggressive Phenotypes in Cancer: Effects of Pharmacological Inhibition on Cell Survival and the Tumor Microenvironment"
(2026).
Biotechnology, Biology and Medicine Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:h7ejy4fg/
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