Hand1 overexpression inhibits medulloblastoma metastasis

Swapna Asuthkar, Maheedhara R. Guda, Sarah E. Martin, Reuben Antony, Karen Fernandez, Julian Lin, Andrew J. Tsung, Kiran K. Velpula

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis.

Original languageEnglish (US)
Pages (from-to)215-221
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume477
Issue number2
DOIs
StatePublished - Aug 19 2016
Externally publishedYes

Fingerprint

Catenins
Medulloblastoma
Cadherins
Neoplasm Metastasis
Basic Helix-Loop-Helix Transcription Factors
Pediatrics
Chemotherapy
Ionizing radiation
Biomarkers
Stem cells
Epithelial-Mesenchymal Transition
Refractory materials
Surgery
Data mining
Tumors
Brain
Radiation
Antibodies
Pluripotent Stem Cells
Data Mining

Keywords

  • EMT
  • Hand1
  • Medulloblastoma
  • Metastasis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Asuthkar, S., Guda, M. R., Martin, S. E., Antony, R., Fernandez, K., Lin, J., ... Velpula, K. K. (2016). Hand1 overexpression inhibits medulloblastoma metastasis. Biochemical and Biophysical Research Communications, 477(2), 215-221. https://doi.org/10.1016/j.bbrc.2016.06.045

Hand1 overexpression inhibits medulloblastoma metastasis. / Asuthkar, Swapna; Guda, Maheedhara R.; Martin, Sarah E.; Antony, Reuben; Fernandez, Karen; Lin, Julian; Tsung, Andrew J.; Velpula, Kiran K.

In: Biochemical and Biophysical Research Communications, Vol. 477, No. 2, 19.08.2016, p. 215-221.

Research output: Contribution to journalArticle

Asuthkar, S, Guda, MR, Martin, SE, Antony, R, Fernandez, K, Lin, J, Tsung, AJ & Velpula, KK 2016, 'Hand1 overexpression inhibits medulloblastoma metastasis', Biochemical and Biophysical Research Communications, vol. 477, no. 2, pp. 215-221. https://doi.org/10.1016/j.bbrc.2016.06.045
Asuthkar, Swapna ; Guda, Maheedhara R. ; Martin, Sarah E. ; Antony, Reuben ; Fernandez, Karen ; Lin, Julian ; Tsung, Andrew J. ; Velpula, Kiran K. / Hand1 overexpression inhibits medulloblastoma metastasis. In: Biochemical and Biophysical Research Communications. 2016 ; Vol. 477, No. 2. pp. 215-221.
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