Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3

Hsiao-Yun Chen; Liang-Ting Lin; Mong-Lien Wang; Benoit Laurent; Chih-Hung Hsu; Chih-Ming Pan; Wan-Ru Jiang; Pau-Yuan Chen; Hsin-I Ma; Yi-Wei Chen; Pin-I Huang; Arthur Chiou; Shih-Hwa Chiou

doi:10.1038/s41598-017-09504-7

Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3

Sci Rep. 2017 Aug 18;7(1):8710. doi: 10.1038/s41598-017-09504-7.

Authors

Hsiao-Yun Chen¹, Liang-Ting Lin^{2

3

4}, Mong-Lien Wang^{2

5}, Benoit Laurent⁶, Chih-Hung Hsu^{6

7}, Chih-Ming Pan^{5

8}, Wan-Ru Jiang³, Pau-Yuan Chen⁹, Hsin-I Ma¹⁰, Yi-Wei Chen^{1

11}, Pin-I Huang^{1

11}, Arthur Chiou¹², Shih-Hwa Chiou^{13

14

15

16

17}

Affiliations

¹ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
² Stem Cell Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
³ Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
⁴ Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
⁵ Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
⁶ Boston Children Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Program in Epigenetic and Molecular Cell Biology, School of Medicine and Public Health, Zhejiang University, Hangzhou, China.
⁸ Center for Cell Therapy, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
⁹ Institute of Biomedical Engineering, National Chiao-Tung University, Hsinchu, Taiwan.
¹⁰ Department of Neurological Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.
¹¹ Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.
¹² Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan.
¹³ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. shchiou@vghtpe.gov.tw.
¹⁴ Stem Cell Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. shchiou@vghtpe.gov.tw.
¹⁵ Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. shchiou@vghtpe.gov.tw.
¹⁶ Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan. shchiou@vghtpe.gov.tw.
¹⁷ Genomic Research Center, Academia Sinica, Taipei, Taiwan. shchiou@vghtpe.gov.tw.

Abstract

The RNA-binding protein Musashi-1 (MSI1) exerts essential roles in multiple cellular functions, such as maintenance of self-renewal and pluripotency of stem cells. MSI1 overexpression has been observed in several tumor tissues, including glioblastoma (GBM), and is considered as a well-established marker for tumor metastasis and recurrence. However, the molecular mechanisms by which MSI1 regulates cell migration are still undetermined. Here we reported that MSI1 alters cell morphology, promotes cell migration, and increases viscoelasticity of GBM cells. We also found that MSI1 directly binds to the 3'UTR of Tensin 3 (TNS3) mRNA, a negative regulator of cell migration, to inhibit its translation. Additionally, we identified that RhoA-GTP could be a potential regulator in MSI1/TNS3-mediated cell migration and morphological changes. In a xenograft animal model, high expression ratio of MSI1 to TNS3 enhanced GBM tumor migration. We also confirmed that MSI1 and TNS3 expressions are mutually exclusive in migratory tumor lesions, and GBM patients with MSI1^high/TNS3^low pattern tend to have poor clinical outcome. Taken together, our findings suggested a critical role of MSI1-TNS3 axis in regulating GBM migration and highlighted that the ratio of MSI1/TNS3 could predict metastatic and survival outcome of GBM patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / genetics
Animals
Cell Adhesion
Cell Line, Tumor
Cell Movement*
Cytoskeleton / metabolism*
Disease Progression
Elasticity
Gene Ontology
Glioblastoma / pathology*
Guanosine Triphosphate / metabolism
Humans
Male
Mice, Inbred BALB C
Mice, Nude
Nerve Tissue Proteins / metabolism*
Protein Binding
Protein Biosynthesis*
RNA-Binding Proteins / metabolism*
Signal Transduction
Tensins / metabolism*
Viscosity
rhoA GTP-Binding Protein / metabolism

Substances

3' Untranslated Regions
MSI1 protein, human
Nerve Tissue Proteins
RNA-Binding Proteins
TNS3 protein, human
Tensins
Guanosine Triphosphate
rhoA GTP-Binding Protein