Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer

Xiao Yang Wang, Huina Yu, R. Ilona Linnoila, Laodong Li, Dangyu Li, Biwen Mo, Hideyuki Okano, Luiz O F Penalva, Robert I. Glazer

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Lung cancer remains one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 20%. One approach to improving survival is the identification of biomarkers to detect early stage disease. In this study, we investigated the potential of the stem cell and progenitor cell marker, Musashi1 (Msi1), as a diagnostic marker and potential therapeutic target for lung cancer. Functional studies in A549 bronchioalveolar carcinoma and NCI-H520 squamous cell carcinoma cells revealed that Msi1 was enriched in spheroid cultures of tumor cells and in the CD133+ cell population. Downregulation of Msi1 by lentivirus-mediated expression of an Msi1 shRNA reduced spheroid colony proliferation. Growth inhibition was associated with reduced nuclear localization of β-catenin and inhibition of the processing of intracellular Notch. In primary lung cancer, Msi1 protein expression was elevated in 86% of 202 tissue microarray specimens, and Msi1 mRNA was increased in 80% of 118 bronchoscopic biopsies, including metastatic disease, but was rarely detected in adjacent normal lung tissue and in non-malignant diseased tissue. Msi1 was expressed in a diffuse pattern in most tumor subtypes, except in squamous cell carcinomas, where it appeared in a focal pattern in 50% of specimens. Thus, Msi1 is a sensitive and specific diagnostic marker for all lung cancer subtypes.

Original languageEnglish
Pages (from-to)739-750
Number of pages12
JournalOncotarget
Volume4
Issue number5
Publication statusPublished - 2013 May

Fingerprint

Lung Neoplasms
Squamous Cell Carcinoma
Stem Cells
Catenins
Neoplasms
Lentivirus
Therapeutics
Small Interfering RNA
Down-Regulation
Cell Culture Techniques
Biomarkers
Carcinoma
Biopsy
Lung
Messenger RNA
Growth
Population
Proteins

Keywords

  • β-catenin
  • Lung cancer
  • Musashi1
  • Notch
  • Numb
  • ShRNA

ASJC Scopus subject areas

  • Oncology

Cite this

Wang, X. Y., Yu, H., Linnoila, R. I., Li, L., Li, D., Mo, B., ... Glazer, R. I. (2013). Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer. Oncotarget, 4(5), 739-750.

Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer. / Wang, Xiao Yang; Yu, Huina; Linnoila, R. Ilona; Li, Laodong; Li, Dangyu; Mo, Biwen; Okano, Hideyuki; Penalva, Luiz O F; Glazer, Robert I.

In: Oncotarget, Vol. 4, No. 5, 05.2013, p. 739-750.

Research output: Contribution to journalArticle

Wang, XY, Yu, H, Linnoila, RI, Li, L, Li, D, Mo, B, Okano, H, Penalva, LOF & Glazer, RI 2013, 'Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer', Oncotarget, vol. 4, no. 5, pp. 739-750.
Wang XY, Yu H, Linnoila RI, Li L, Li D, Mo B et al. Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer. Oncotarget. 2013 May;4(5):739-750.
Wang, Xiao Yang ; Yu, Huina ; Linnoila, R. Ilona ; Li, Laodong ; Li, Dangyu ; Mo, Biwen ; Okano, Hideyuki ; Penalva, Luiz O F ; Glazer, Robert I. / Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer. In: Oncotarget. 2013 ; Vol. 4, No. 5. pp. 739-750.
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