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Musashi–1—A Stemness RBP for Cancer Therapy?

N. Bley,Ali Hmedat,Simon Müller,R. Rolnik,Alexander Rausch,M. Lederer,S. Hüttelmaier

Published 2021 in Biology

ABSTRACT

Simple Summary Musashi–1 (MSI1) is an RNA–binding protein that promotes stemness properties. It was initially discovered as a regulator of neuronal development and oocyte maturation in flies and frogs. Due to its specific expression pattern with high levels during development and in a variety of cancers, MSI1 evolved as an interesting target for cancer therapy. In cancer cells, the protein mainly promotes an undifferentiated state enhancing cancer growth and therapy resistance. In this review, we summarize previous findings from development of other organisms, outline MSI1′s expression and function in different cancer entities and highlight the development of MSI1–directed inhibitors. Abstract The RNA–binding protein Musashi–1 (MSI1) promotes stemness during development and cancer. By controlling target mRNA turnover and translation, MSI1 is implicated in the regulation of cancer hallmarks such as cell cycle or Notch signaling. Thereby, the protein enhanced cancer growth and therapy resistance to standard regimes. Due to its specific expression pattern and diverse functions, MSI1 represents an interesting target for cancer therapy in the future. In this review we summarize previous findings on MSI1′s implications in developmental processes of other organisms. We revisit MSI1′s expression in a set of solid cancers, describe mechanistic details and implications in MSI1 associated cancer hallmark pathways and highlight current research in drug development identifying the first MSI1–directed inhibitors with anti–tumor activity.

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