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

05-16-2023

“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: https://doi.org/10.18632/aging.204620 

Corresponding Author: Pranela Rameshwar

Corresponding Email: rameshwa@njms.rutgers.edu 

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

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About Aging-US:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed CentralWeb of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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