1 Citation (Scopus)

Abstract

Glioblastoma multiforme (GBM) is a lethal brain tumor with a mean survival time of 1 year. One major reason for therapeutic failure is that GBM cells have an extraordinary capacity to invade normal brain tissue beyond the surgical margin, accounting for the lack of treatment efficacy. GBM cells that can infiltrate into the healthy brain possess tumor properties of stemness and invasion, and previous studies demonstrate that Musashi-1 (MSI1), a neural stem cell marker, plays an important role in the maintenance of stem cell status, cellular differentiation, and tumorigenesis in cancers. By analyzing neuronal progenitor cell markers and stemness genes, we predicted that MSI1 might be an important factor in GBM pathogenesis. Because inflammation aids in the proliferation and survival of malignant cells, the inflammatory microenvironment also promotes GBM invasion, and intercellular adhesion molecule-1 (ICAM1), a member of the immunoglobulin superfamily, is involved in inflammation. Our results indicate that the above phenomena are likely due to MSI1 upregulation, which occurred simultaneously with higher expression of ICAM1 in GBM cells. Indeed, MSI1 knockdown effectively suppressed ICAM1 expression and blocked GBM cell motility and invasion, whereas overexpressing ICAM1 reversed these effects. According to RNA immunoprecipitation assays, MSI1-mediated mRNA interactions promote ICAM1 translation. Finally, immunohistochemical analysis showed MSI1 and ICAM-1 to be coexpressed at high levels in GBM tissues. Thus, the MSI1/ICAM1 pathway plays an important role in oncogenic resistance, including increased tumor invasion, and MSI1/ICAM1 may be a target for GBM treatment.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalNeoplasia (United States)
Volume21
Issue number5
DOIs
Publication statusPublished - May 1 2019

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Intercellular Adhesion Molecule-1
Glioblastoma
Brain Neoplasms
Stem Cells
Inflammation
Cellular Microenvironment
Neural Stem Cells
Immunoprecipitation
Cell Movement
Immunoglobulins
Neoplasms
Carcinogenesis
Up-Regulation
Maintenance
RNA
Messenger RNA
Brain

ASJC Scopus subject areas

  • Cancer Research

Cite this

Musashi-1 Enhances Glioblastoma Migration by Promoting ICAM1 Translation. / Lin, Jang Chun; Tsai, Jo Ting; Chao, Tsu Yi; Ma, Hsin I.; Liu, Wei Hsiu.

In: Neoplasia (United States), Vol. 21, No. 5, 01.05.2019, p. 459-468.

Research output: Contribution to journalArticle

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