Abstract

Simple SummaryMusashi–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.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.

Highlights

  • RNA–binding proteins (RBPs) control all aspects of post–transcriptional gene expression, including RNA splicing and editing, transport and localization, mRNA turnover and translation as well as miRNA biogenesis [1,2]

  • In contrast to MSI2, for which oncogenic potential and expression was predominantly reported in leukemia, MSI1 expression was shown in a variety of human cancers, primarily solid cancers [57]

  • For KEGG: Cell_cycle and KEGG: Basal_cell_carcinoma, we found the highest conservation with significant associations in 11 out of 18 (61%) of analyzed cancer entities and 100% or 75% conservation among the top four MSI1 de–regulated cancers

Read more

Summary

Introduction

RNA–binding proteins (RBPs) control all aspects of post–transcriptional gene expression, including RNA splicing and editing, transport and localization, mRNA turnover and translation as well as miRNA biogenesis [1,2]. They play essential roles during development, and serve essential roles in tumor biology by modulating essentially all hallmarks of cancer [2,3]. GLD2a to target mRNAssignal tion In motifs (RRMs) MSI1 in the N–terminal region,toeach containing nuclear localization in Xenopus oocytes, (NLS, resulting cytoplasmic poly–adenylation to induce and fosFigurein1)elevated [12,13]. 0 untranslated translational regulation instructures, cancer cells needs to consider function and region) external hairpin located preferentially withinthis the 3dual of target guidance cues, requiring further transcripts [16]. in–depth investigation

Structure theprotein
Role in Development
Expression in Human Tissue
30 March by
Expression and Prognostic Value in Solid Human Cancers
MSI1 as a Modulator of Cancer Hallmarks
Conserved Pathways in Solid Human Cancers
A Signaling Regulator in Female Cancers
Control of MSI1 Expression in Cancer
Targeting Musashi–1 in Cancer
Findings
Conclusions
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call