Research ExplorerPublicationsBeta-catenin-induced melanoma growth requires the downstream...

Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor

Standard

Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. / Widlund, Hans R; Horstmann, Martin A; Price, E Roydon; Cui, Junqing; Lessnick, Stephen L; Wu, Min; He, Xi; Fisher, David E.

In: J CELL BIOL, Vol. 158, No. 6, 16.09.2002, p. 1079-87.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Widlund, HR, Horstmann, MA, Price, ER, Cui, J, Lessnick, SL, Wu, M, He, X & Fisher, DE 2002, 'Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor', J CELL BIOL, vol. 158, no. 6, pp. 1079-87. https://doi.org/10.1083/jcb.200202049

APA

Widlund, H. R., Horstmann, M. A., Price, E. R., Cui, J., Lessnick, S. L., Wu, M., He, X., & Fisher, D. E. (2002). Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. J CELL BIOL, 158(6), 1079-87. https://doi.org/10.1083/jcb.200202049

Vancouver

Widlund HR, Horstmann MA, Price ER, Cui J, Lessnick SL, Wu M et al. Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. J CELL BIOL. 2002 Sep 16;158(6):1079-87. https://doi.org/10.1083/jcb.200202049

Bibtex

@article{d27e204e51e744e5a1f7a7827c1659a8,
title = "Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor",
abstract = "The transcription factor Microphthalmia-associated transcription factor (MITF) is a lineage-determination factor, which modulates melanocyte differentiation and pigmentation. MITF was recently shown to reside downstream of the canonical Wnt pathway during melanocyte differentiation from pluripotent neural crest cells in zebrafish as well as in mammalian melanocyte lineage cells. Although expression of many melanocytic/pigmentation markers is lost in human melanoma, MITF expression remains intact, even in unpigmented tumors, suggesting a role for MITF beyond its role in differentiation. A significant fraction of primary human melanomas exhibit deregulation (via aberrant nuclear accumulation) of beta-catenin, leading us to examine its role in melanoma growth and survival. Here, we show that beta-catenin is a potent mediator of growth for melanoma cells in a manner dependent on its downstream target MITF. Moreover, suppression of melanoma clonogenic growth by disruption of beta-catenin-T-cell transcription factor/LEF is rescued by constitutive MITF. This rescue occurs largely through a prosurvival mechanism. Thus, beta-catenin regulation of MITF expression represents a tissue-restricted pathway that significantly influences the growth and survival behavior of this notoriously treatment-resistant neoplasm.",
keywords = "Animals, Apoptosis, Cell Division, Cell Line, Cytoskeletal Proteins, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Green Fluorescent Proteins, Humans, Luminescent Proteins, Lymphoid Enhancer-Binding Factor 1, Melanoma, Melanoma, Experimental, Mice, Microphthalmia-Associated Transcription Factor, Promoter Regions, Genetic, Trans-Activators, Transcription Factors, Transcriptional Activation, Transfection, Tumor Cells, Cultured, beta Catenin",
author = "Widlund, {Hans R} and Horstmann, {Martin A} and Price, {E Roydon} and Junqing Cui and Lessnick, {Stephen L} and Min Wu and Xi He and Fisher, {David E}",
year = "2002",
month = sep,
day = "16",
doi = "10.1083/jcb.200202049",
language = "English",
volume = "158",
pages = "1079--87",
journal = "J CELL BIOL",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",

}

RIS

TY - JOUR

T1 - Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor

AU - Widlund, Hans R

AU - Horstmann, Martin A

AU - Price, E Roydon

AU - Cui, Junqing

AU - Lessnick, Stephen L

AU - Wu, Min

AU - He, Xi

AU - Fisher, David E

PY - 2002/9/16

Y1 - 2002/9/16

N2 - The transcription factor Microphthalmia-associated transcription factor (MITF) is a lineage-determination factor, which modulates melanocyte differentiation and pigmentation. MITF was recently shown to reside downstream of the canonical Wnt pathway during melanocyte differentiation from pluripotent neural crest cells in zebrafish as well as in mammalian melanocyte lineage cells. Although expression of many melanocytic/pigmentation markers is lost in human melanoma, MITF expression remains intact, even in unpigmented tumors, suggesting a role for MITF beyond its role in differentiation. A significant fraction of primary human melanomas exhibit deregulation (via aberrant nuclear accumulation) of beta-catenin, leading us to examine its role in melanoma growth and survival. Here, we show that beta-catenin is a potent mediator of growth for melanoma cells in a manner dependent on its downstream target MITF. Moreover, suppression of melanoma clonogenic growth by disruption of beta-catenin-T-cell transcription factor/LEF is rescued by constitutive MITF. This rescue occurs largely through a prosurvival mechanism. Thus, beta-catenin regulation of MITF expression represents a tissue-restricted pathway that significantly influences the growth and survival behavior of this notoriously treatment-resistant neoplasm.

AB - The transcription factor Microphthalmia-associated transcription factor (MITF) is a lineage-determination factor, which modulates melanocyte differentiation and pigmentation. MITF was recently shown to reside downstream of the canonical Wnt pathway during melanocyte differentiation from pluripotent neural crest cells in zebrafish as well as in mammalian melanocyte lineage cells. Although expression of many melanocytic/pigmentation markers is lost in human melanoma, MITF expression remains intact, even in unpigmented tumors, suggesting a role for MITF beyond its role in differentiation. A significant fraction of primary human melanomas exhibit deregulation (via aberrant nuclear accumulation) of beta-catenin, leading us to examine its role in melanoma growth and survival. Here, we show that beta-catenin is a potent mediator of growth for melanoma cells in a manner dependent on its downstream target MITF. Moreover, suppression of melanoma clonogenic growth by disruption of beta-catenin-T-cell transcription factor/LEF is rescued by constitutive MITF. This rescue occurs largely through a prosurvival mechanism. Thus, beta-catenin regulation of MITF expression represents a tissue-restricted pathway that significantly influences the growth and survival behavior of this notoriously treatment-resistant neoplasm.

KW - Animals

KW - Apoptosis

KW - Cell Division

KW - Cell Line

KW - Cytoskeletal Proteins

KW - DNA-Binding Proteins

KW - Gene Expression Regulation, Neoplastic

KW - Green Fluorescent Proteins

KW - Humans

KW - Luminescent Proteins

KW - Lymphoid Enhancer-Binding Factor 1

KW - Melanoma

KW - Melanoma, Experimental

KW - Mice

KW - Microphthalmia-Associated Transcription Factor

KW - Promoter Regions, Genetic

KW - Trans-Activators

KW - Transcription Factors

KW - Transcriptional Activation

KW - Transfection

KW - Tumor Cells, Cultured

KW - beta Catenin

U2 - 10.1083/jcb.200202049

DO - 10.1083/jcb.200202049

M3 - SCORING: Journal article

C2 - 12235125

VL - 158

SP - 1079

EP - 1087

JO - J CELL BIOL

JF - J CELL BIOL

SN - 0021-9525

IS - 6

ER -