Musashi 1 in Breast Cancer: Implications for Dormancy and Survival in Bone Marrow

“This study now links Msi 1 to PD-L1.”

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BUFFALO, NY- May 16, 2023 – A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 15, Issue 9, entitled, “Increased expression of musashi 1 on breast cancer cells has implication to understand dormancy and survival in bone marrow.”

Breast cancer (BC) stem cells (CSCs) resist treatment and can exist as dormant cells in tissues such as the bone marrow (BM). Years before clinical diagnosis, BC cells (BCCs) could migrate from the primary site where the BM niche cells facilitate dedifferentiation into CSCs. Additionally, dedifferentiation could occur by cell autonomous methods. 

In this new study, researchers George R. Nahas, Lauren S. Sherman, Garima Sinha, Markos H. El Far, Andrew Petryna, Steven M. Munoz, Kimberly A. Silverio, Maran Shaker, Pujan Neopane, Veronica Mariotti, and Pranela Rameshwar from Rutgers New Jersey Medical School studied the role of the RNA-binding protein, Musashi I (Msi 1). They also analyzed its relationship with the T-cell inhibitory molecule programmed death-ligand 1 (PD-L1) in CSCs.

“We validated the link between Msi 1 and PD-L1 in CSCs [cancer stem cells] based on significant reduction of CSCs following Msi 1 knockdown.”

PD-L1 is expressed on triple negative BC and other cancers. Therefore, PD-L1 is an immune checkpoint that is a target in immune therapy for cancers. Msi 1 can support BCC growth through stabilization of oncogenic transcripts and modulation of stem cell-related gene expression. The researchers reported on a role for Msi 1 to maintain CSCs. They found that it seemed to occur by the differentiation of CSCs to more matured BCCs. This correlated with increased transition from cycling quiescence and reduced expression of stem cell-linked genes. CSCs co-expressed Msi 1 and PD-L1. Msi 1 knockdown led to a significant decrease in CSCs with undetectable PD-L1. 

“This study has implications for Msi 1 as a therapeutic target, in combination with [an] immune checkpoint inhibitor. Such treatment could also prevent dedifferentiation of breast cancer to CSCs, and to reverse tumor dormancy. The proposed combined treatment might be appropriate for other solid tumors.”

Read the full study: DOI: 

Corresponding Author: Pranela Rameshwar

Corresponding Email: [email protected] 

Keywords: cancer stem cell, breast cancer, musashi 1, bone marrow, dormancy

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Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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