TGF-β induces SOX2 expression in a time-dependent manner in human melanoma cells
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TGF-β induces SOX2 expression in a time-dependent manner in human melanoma cells. / Weina, Kasia; Wu, Huizi; Knappe, Nathalie; Orouji, Elias; Novak, Daniel; Bernhardt, Mathias; Hüser, Laura; Larribère, Lionel; Umansky, Viktor; Gebhardt, Christoffer; Utikal, Jochen.
In: PIGM CELL MELANOMA R, Vol. 29, No. 4, 07.2016, p. 453-458.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - TGF-β induces SOX2 expression in a time-dependent manner in human melanoma cells
AU - Weina, Kasia
AU - Wu, Huizi
AU - Knappe, Nathalie
AU - Orouji, Elias
AU - Novak, Daniel
AU - Bernhardt, Mathias
AU - Hüser, Laura
AU - Larribère, Lionel
AU - Umansky, Viktor
AU - Gebhardt, Christoffer
AU - Utikal, Jochen
N1 - © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2016/7
Y1 - 2016/7
N2 - The sry-related high-mobility box (SOX)-2 protein has recently been proven to play a significant role in progression, metastasis, and clinical prognosis spanning several cancer types. Research on the role of SOX2 in melanoma is limited and currently little is known about the mechanistic function of this gene in this context. Here, we observed high expression of SOX2 in both human melanoma cell lines and primary melanomas in contrast to melanocytic nevi. This overexpression in melanoma can, in part, be explained by extra gene copy numbers of SOX2 in primary samples. Interestingly, we were able to induce SOX2 expression, mediated by SOX4, via TGF-β1 stimulation in a time-dependent manner. Moreover, the knockdown of SOX2 impaired TGF-β-induced invasiveness. This phenotype switch can be explained by SOX2-mediated cross talk between TGF-β and non-canonical Wnt signaling. Thus, we propose that SOX2 is involved in the critical TGF-β signaling pathway, which has been shown to correlate with melanoma aggressiveness and metastasis. In conclusion, we have identified a novel downstream factor of TGF-β signaling in melanoma, which may have further implications in the clinic.
AB - The sry-related high-mobility box (SOX)-2 protein has recently been proven to play a significant role in progression, metastasis, and clinical prognosis spanning several cancer types. Research on the role of SOX2 in melanoma is limited and currently little is known about the mechanistic function of this gene in this context. Here, we observed high expression of SOX2 in both human melanoma cell lines and primary melanomas in contrast to melanocytic nevi. This overexpression in melanoma can, in part, be explained by extra gene copy numbers of SOX2 in primary samples. Interestingly, we were able to induce SOX2 expression, mediated by SOX4, via TGF-β1 stimulation in a time-dependent manner. Moreover, the knockdown of SOX2 impaired TGF-β-induced invasiveness. This phenotype switch can be explained by SOX2-mediated cross talk between TGF-β and non-canonical Wnt signaling. Thus, we propose that SOX2 is involved in the critical TGF-β signaling pathway, which has been shown to correlate with melanoma aggressiveness and metastasis. In conclusion, we have identified a novel downstream factor of TGF-β signaling in melanoma, which may have further implications in the clinic.
KW - Cells, Cultured
KW - Disease Progression
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Melanoma
KW - Nevus, Pigmented
KW - SOXB1 Transcription Factors
KW - SOXC Transcription Factors
KW - Signal Transduction
KW - Skin Neoplasms
KW - Time Factors
KW - Transforming Growth Factor beta1
KW - Journal Article
U2 - 10.1111/pcmr.12483
DO - 10.1111/pcmr.12483
M3 - SCORING: Journal article
C2 - 27105574
VL - 29
SP - 453
EP - 458
JO - PIGM CELL MELANOMA R
JF - PIGM CELL MELANOMA R
SN - 1755-1471
IS - 4
ER -