The role of melanogenesis in regulation of melanoma behavior

Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

A. Slominski, T. K. Kim, A. A. Brozyna, Z. Janjetovic, D. L.P. Brooks, L. P. Schwab, C. Skobowiat, W. Jóźwicki, Tiffany Seagroves

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

To study the effect of melanogenesis on HIF-1α expression and attendant pathways, we used stable human and hamster melanoma cell lines in which the amelanotic vs. melanotic phenotypes are dependent upon the concentration of melanogenesis precursors in the culture media. The induction of melanin pigmentation led to significant up-regulation of HIF-1α, but not HIF-2α, protein in melanized cells for both lines. Similar upregulation of nuclear HIF-1α was observed in excisions of advanced melanotic vs. amelanotic melanomas. In cultured cells, melanogenesis also significantly stimulated expression of classical HIF-1-dependent target genes involved in angiogenesis and cellular metabolism, including glucose metabolism and stimulation of activity of key enzymes in the glycolytic pathway. Several other stress related genes containing putative HRE consensus sites were also upregulated by melanogenesis, concurrently with modulation of expression of HIF-1-independent genes encoding for steroidogenic enzymes, cytokines and growth factors. Immunohistochemical studies using a large panel of pigmented lesions revealed that higher levels of HIF-1α and GLUT-1 were detected in advanced melanomas in comparison to melanocytic nevi or thin melanomas localized to the skin. However, the effects on overall or disease free survival in melanoma patients were modest or absent for GLUT-1 or for HIF-1α, respectively. In conclusion, induction of the melanogenic pathway leads to robust upregulation of HIF-1-dependent and independent pathways in cultured melanoma cells, suggesting a key role for melanogenesis in regulation of cellular metabolism.

Original languageEnglish (US)
Pages (from-to)79-93
Number of pages15
JournalArchives of Biochemistry and Biophysics
Volume563
DOIs
StatePublished - Dec 15 2014

Fingerprint

Metabolism
Melanoma
Genes
Cells
Up-Regulation
Gene encoding
Melanins
Enzymes
Cultured Cells
Culture Media
Amelanotic Melanoma
Intercellular Signaling Peptides and Proteins
Skin
Pigmented Nevus
Cell Line
Modulation
Cytokines
Pigmentation
Glucose
Cricetinae

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

The role of melanogenesis in regulation of melanoma behavior : Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways. / Slominski, A.; Kim, T. K.; Brozyna, A. A.; Janjetovic, Z.; Brooks, D. L.P.; Schwab, L. P.; Skobowiat, C.; Jóźwicki, W.; Seagroves, Tiffany.

In: Archives of Biochemistry and Biophysics, Vol. 563, 15.12.2014, p. 79-93.

Research output: Contribution to journalArticle

Slominski, A. ; Kim, T. K. ; Brozyna, A. A. ; Janjetovic, Z. ; Brooks, D. L.P. ; Schwab, L. P. ; Skobowiat, C. ; Jóźwicki, W. ; Seagroves, Tiffany. / The role of melanogenesis in regulation of melanoma behavior : Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways. In: Archives of Biochemistry and Biophysics. 2014 ; Vol. 563. pp. 79-93.
@article{f87cf5c43e1d407a82d2141366e70984,
title = "The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways",
abstract = "To study the effect of melanogenesis on HIF-1α expression and attendant pathways, we used stable human and hamster melanoma cell lines in which the amelanotic vs. melanotic phenotypes are dependent upon the concentration of melanogenesis precursors in the culture media. The induction of melanin pigmentation led to significant up-regulation of HIF-1α, but not HIF-2α, protein in melanized cells for both lines. Similar upregulation of nuclear HIF-1α was observed in excisions of advanced melanotic vs. amelanotic melanomas. In cultured cells, melanogenesis also significantly stimulated expression of classical HIF-1-dependent target genes involved in angiogenesis and cellular metabolism, including glucose metabolism and stimulation of activity of key enzymes in the glycolytic pathway. Several other stress related genes containing putative HRE consensus sites were also upregulated by melanogenesis, concurrently with modulation of expression of HIF-1-independent genes encoding for steroidogenic enzymes, cytokines and growth factors. Immunohistochemical studies using a large panel of pigmented lesions revealed that higher levels of HIF-1α and GLUT-1 were detected in advanced melanomas in comparison to melanocytic nevi or thin melanomas localized to the skin. However, the effects on overall or disease free survival in melanoma patients were modest or absent for GLUT-1 or for HIF-1α, respectively. In conclusion, induction of the melanogenic pathway leads to robust upregulation of HIF-1-dependent and independent pathways in cultured melanoma cells, suggesting a key role for melanogenesis in regulation of cellular metabolism.",
author = "A. Slominski and Kim, {T. K.} and Brozyna, {A. A.} and Z. Janjetovic and Brooks, {D. L.P.} and Schwab, {L. P.} and C. Skobowiat and W. J{\'o}źwicki and Tiffany Seagroves",
year = "2014",
month = "12",
day = "15",
doi = "10.1016/j.abb.2014.06.030",
language = "English (US)",
volume = "563",
pages = "79--93",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - The role of melanogenesis in regulation of melanoma behavior

T2 - Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

AU - Slominski, A.

AU - Kim, T. K.

AU - Brozyna, A. A.

AU - Janjetovic, Z.

AU - Brooks, D. L.P.

AU - Schwab, L. P.

AU - Skobowiat, C.

AU - Jóźwicki, W.

AU - Seagroves, Tiffany

PY - 2014/12/15

Y1 - 2014/12/15

N2 - To study the effect of melanogenesis on HIF-1α expression and attendant pathways, we used stable human and hamster melanoma cell lines in which the amelanotic vs. melanotic phenotypes are dependent upon the concentration of melanogenesis precursors in the culture media. The induction of melanin pigmentation led to significant up-regulation of HIF-1α, but not HIF-2α, protein in melanized cells for both lines. Similar upregulation of nuclear HIF-1α was observed in excisions of advanced melanotic vs. amelanotic melanomas. In cultured cells, melanogenesis also significantly stimulated expression of classical HIF-1-dependent target genes involved in angiogenesis and cellular metabolism, including glucose metabolism and stimulation of activity of key enzymes in the glycolytic pathway. Several other stress related genes containing putative HRE consensus sites were also upregulated by melanogenesis, concurrently with modulation of expression of HIF-1-independent genes encoding for steroidogenic enzymes, cytokines and growth factors. Immunohistochemical studies using a large panel of pigmented lesions revealed that higher levels of HIF-1α and GLUT-1 were detected in advanced melanomas in comparison to melanocytic nevi or thin melanomas localized to the skin. However, the effects on overall or disease free survival in melanoma patients were modest or absent for GLUT-1 or for HIF-1α, respectively. In conclusion, induction of the melanogenic pathway leads to robust upregulation of HIF-1-dependent and independent pathways in cultured melanoma cells, suggesting a key role for melanogenesis in regulation of cellular metabolism.

AB - To study the effect of melanogenesis on HIF-1α expression and attendant pathways, we used stable human and hamster melanoma cell lines in which the amelanotic vs. melanotic phenotypes are dependent upon the concentration of melanogenesis precursors in the culture media. The induction of melanin pigmentation led to significant up-regulation of HIF-1α, but not HIF-2α, protein in melanized cells for both lines. Similar upregulation of nuclear HIF-1α was observed in excisions of advanced melanotic vs. amelanotic melanomas. In cultured cells, melanogenesis also significantly stimulated expression of classical HIF-1-dependent target genes involved in angiogenesis and cellular metabolism, including glucose metabolism and stimulation of activity of key enzymes in the glycolytic pathway. Several other stress related genes containing putative HRE consensus sites were also upregulated by melanogenesis, concurrently with modulation of expression of HIF-1-independent genes encoding for steroidogenic enzymes, cytokines and growth factors. Immunohistochemical studies using a large panel of pigmented lesions revealed that higher levels of HIF-1α and GLUT-1 were detected in advanced melanomas in comparison to melanocytic nevi or thin melanomas localized to the skin. However, the effects on overall or disease free survival in melanoma patients were modest or absent for GLUT-1 or for HIF-1α, respectively. In conclusion, induction of the melanogenic pathway leads to robust upregulation of HIF-1-dependent and independent pathways in cultured melanoma cells, suggesting a key role for melanogenesis in regulation of cellular metabolism.

UR - http://www.scopus.com/inward/record.url?scp=84908450370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908450370&partnerID=8YFLogxK

U2 - 10.1016/j.abb.2014.06.030

DO - 10.1016/j.abb.2014.06.030

M3 - Article

VL - 563

SP - 79

EP - 93

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

ER -