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PDFOpen Access (License Unspecified), Open Access
Thesis
MSX1 reprograms melanocytes into neural crest-like stem cells and promotes melanoma progression
Master of Science (M.S.), Drexel University
Jan 2014
DOI:
https://doi.org/10.17918/etd-4503
Abstract
Differentiation from stem cells to lineage-specific somatic cells is not a unidirectional process, but can be reverted by genetic and/or epigenetic alterations. Here, we show that the homeodomain transcription factor Msh homeobox 1 (MSX1), which is essential for neural crest specification, reprograms melanocytes towards a neural crest precursor-like state. MSX1-expressing melanocytes express the neural crest marker p75 neurotrophin receptor and are able to differentiate into neuronal and mesenchymal lineages. Mechanistically, MSX1 binds and suppresses the proximal promoter of microphthalmia-associated transcription factor (MITF), the master transcriptional regulator of melanogenesis. Expression of MSX1 is significantly correlated with melanoma progression, as overexpression of MSX1 prompts melanoma cell motility and depletion of MSX1 significantly inhibits melanoma migration. Taken together, these results demonstrate that neural crest-like reprogramming in melanocytes can be achieved by a single factor and that similar dedifferentiation is a critical process for melanoma progression.
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Details
- Title
- MSX1 reprograms melanocytes into neural crest-like stem cells and promotes melanoma progression
- Creators
- Joshua X. Wang - DU
- Contributors
- Meenhard Herlyn (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 4503; 991014632848104721