Cargando…

FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells

Metastases are thought to arise from cancer stem cells and their tumor initiating abilities are required for the establishment of metastases. Nevertheless, in metastatic melanoma, the nature of cancer stem cells is under debate and their contribution to metastasis formation remains unknown. Using an...

Descripción completa

Detalles Bibliográficos
Autores principales: Tiwary, Shweta, Xu, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726610/
https://www.ncbi.nlm.nih.gov/pubmed/26808375
http://dx.doi.org/10.1371/journal.pone.0147638
_version_ 1782411856545054720
author Tiwary, Shweta
Xu, Lei
author_facet Tiwary, Shweta
Xu, Lei
author_sort Tiwary, Shweta
collection PubMed
description Metastases are thought to arise from cancer stem cells and their tumor initiating abilities are required for the establishment of metastases. Nevertheless, in metastatic melanoma, the nature of cancer stem cells is under debate and their contribution to metastasis formation remains unknown. Using an experimental metastasis model, we discovered that high levels of the WNT receptor, FZD7, correlated with enhanced metastatic potentials of melanoma cell lines. Knocking down of FZD7 in a panel of four melanoma cell lines led to a significant reduction in lung metastases in animal models, arguing that FZD7 plays a causal role during metastasis formation. Notably, limiting dilution analyses revealed that FZD7 is essential for the tumor initiation of melanoma cells and FZD7 knockdown impeded the early expansion of metastatic melanoma cells shortly after seeding, in accordance with the view that tumor initiating ability of cancer cells is required for metastasis formation. FZD7 activated JNK in melanoma cell lines in vitro and the expression of a dominant negative JNK suppressed metastasis formation in vivo, suggesting that FZD7 may promote metastatic growth of melanoma cells via activation of JNK. Taken together, our findings uncovered a signaling pathway that regulates the tumor initiation of melanoma cells and contributes to metastasis formation in melanoma.
format Online
Article
Text
id pubmed-4726610
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-47266102016-02-03 FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells Tiwary, Shweta Xu, Lei PLoS One Research Article Metastases are thought to arise from cancer stem cells and their tumor initiating abilities are required for the establishment of metastases. Nevertheless, in metastatic melanoma, the nature of cancer stem cells is under debate and their contribution to metastasis formation remains unknown. Using an experimental metastasis model, we discovered that high levels of the WNT receptor, FZD7, correlated with enhanced metastatic potentials of melanoma cell lines. Knocking down of FZD7 in a panel of four melanoma cell lines led to a significant reduction in lung metastases in animal models, arguing that FZD7 plays a causal role during metastasis formation. Notably, limiting dilution analyses revealed that FZD7 is essential for the tumor initiation of melanoma cells and FZD7 knockdown impeded the early expansion of metastatic melanoma cells shortly after seeding, in accordance with the view that tumor initiating ability of cancer cells is required for metastasis formation. FZD7 activated JNK in melanoma cell lines in vitro and the expression of a dominant negative JNK suppressed metastasis formation in vivo, suggesting that FZD7 may promote metastatic growth of melanoma cells via activation of JNK. Taken together, our findings uncovered a signaling pathway that regulates the tumor initiation of melanoma cells and contributes to metastasis formation in melanoma. Public Library of Science 2016-01-25 /pmc/articles/PMC4726610/ /pubmed/26808375 http://dx.doi.org/10.1371/journal.pone.0147638 Text en © 2016 Tiwary, Xu http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Tiwary, Shweta
Xu, Lei
FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells
title FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells
title_full FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells
title_fullStr FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells
title_full_unstemmed FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells
title_short FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells
title_sort frizzled7 is required for tumor inititation and metastatic growth of melanoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726610/
https://www.ncbi.nlm.nih.gov/pubmed/26808375
http://dx.doi.org/10.1371/journal.pone.0147638
work_keys_str_mv AT tiwaryshweta frizzled7isrequiredfortumorinititationandmetastaticgrowthofmelanomacells
AT xulei frizzled7isrequiredfortumorinititationandmetastaticgrowthofmelanomacells