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Doubi, Melpomenie Guissouegou
(2024).
DOI: https://doi.org/10.21954/ou.ro.00096225
Abstract
Breast cancer is the most common form of cancer among women worldwide and still one of the leading causes of cancer-related deaths. This can be attributed primarily to the genetic/epigenetic changes and microenvironmental alterations leading to aggressive and therapy-resistant metastasis. The tumor microenvironment, composed of diverse immune and stromal cells along with the extracellular matrix, significantly influences BC progression with its evolving desmoplastic and immunosuppressive features. Despite significant advancements in immune checkpoint therapies, many patients do not respond and develop resistance to the treatment, emphasizing the need for alternative approaches to enhance responses to these interventions.
Pin1 is a unique phosphorylation-dependent prolyl-isomerase with a crucial role in regulating the structure and function of cellular proteins through cis/trans isomerization of phosphorylated Ser/Thr-Pro motifs. Pin1 levels are elevated in tumors and contribute to the modulation of oncogenic signaling pathways relevant to tumor growth and resistance to therapies. Conversely, reduced Pin1 expression is observed in aging-related and neurodegenerative diseases like Alzheimer's, suggesting opposite roles in cancer and neurodegeneration.
Recent research in our laboratory revealed a novel function of Pin1 in neuronal cells as a regulator of the nuclear envelope under mechanical stress, by modulating the Lamin B structure and the anchoring function of Heterochromatin protein 1α and thus preventing aging-related phenotypes and activation of innate immunity pathways.
Considering that in cancer cells the nucleus is constantly challenged by mechanical cues during tumor growth and invasion, we hypothesize that elevated levels of Pin1 in cancer cells could be crucial for maintaining nuclear integrity and heterochromatin, promoting immunosuppression, and facilitating tumor cell survival and disease progression.
Hence, this study is investigating the mechanisms by which Pin1 depletion could modulate signaling pathways involved in sustaining anti-tumor immune responses.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)
