High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma

Increased or decreased expression of LIF receptor (LIFr) has been reported in several human cancers, including skin cancer, but its role in melanoma is unknown. In this study, we investigated the expression pattern of LIFr in melanoma and assessed its prognostic value. Using tissue microarrays consi...

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Main Authors:	Guo, Hongwei, Cheng, Yabin, Martinka, Magdalena, McElwee, Kevin
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694846/

id	pubmed-4694846
recordtype	oai_dc
spelling	pubmed-46948462016-01-20 High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma Guo, Hongwei Cheng, Yabin Martinka, Magdalena McElwee, Kevin Research Paper Increased or decreased expression of LIF receptor (LIFr) has been reported in several human cancers, including skin cancer, but its role in melanoma is unknown. In this study, we investigated the expression pattern of LIFr in melanoma and assessed its prognostic value. Using tissue microarrays consisting of 441 melanomas and 96 nevi, we found that no normal nevi showed high LIFr expression. LIFr staining was significantly increased in primary melanoma compared to dysplastic nevi (P = 0.0003) and further increased in metastatic melanoma (P = 0.0000). Kaplan–Meier survival curve and univariate Cox regression analyses showed that increased expression of LIFr was correlated with poorer 5-year patient survival (overall survival, P = 0.0000; disease-specific survival, P = 0.0000). Multivariate Cox regression analyses indicated that increased LIFr expression was an independent prognostic marker for primary melanoma (P = 0.036). LIFr knockdown inhibited melanoma cell migration in wound healing assays and reduced stress fiber formation. LIFr knockdown correlated with STAT3 suppression, but not YAP, suggesting that LIFr activation might stimulate melanoma cell migration through the STAT3 pathway. Our data indicate that strong LIFr expression identifies potentially highly malignant melanocytic lesions at an early stage and LIFr may be a potential target for the development of early intervention therapeutics. Impact Journals LLC 2015-07-25 /pmc/articles/PMC4694846/ /pubmed/26329521 Text en Copyright: © 2015 Guo et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Guo, Hongwei Cheng, Yabin Martinka, Magdalena McElwee, Kevin
spellingShingle	Guo, Hongwei Cheng, Yabin Martinka, Magdalena McElwee, Kevin High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma
author_facet	Guo, Hongwei Cheng, Yabin Martinka, Magdalena McElwee, Kevin
author_sort	Guo, Hongwei
title	High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma
title_short	High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma
title_full	High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma
title_fullStr	High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma
title_full_unstemmed	High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma
title_sort	high lifr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma
description	Increased or decreased expression of LIF receptor (LIFr) has been reported in several human cancers, including skin cancer, but its role in melanoma is unknown. In this study, we investigated the expression pattern of LIFr in melanoma and assessed its prognostic value. Using tissue microarrays consisting of 441 melanomas and 96 nevi, we found that no normal nevi showed high LIFr expression. LIFr staining was significantly increased in primary melanoma compared to dysplastic nevi (P = 0.0003) and further increased in metastatic melanoma (P = 0.0000). Kaplan–Meier survival curve and univariate Cox regression analyses showed that increased expression of LIFr was correlated with poorer 5-year patient survival (overall survival, P = 0.0000; disease-specific survival, P = 0.0000). Multivariate Cox regression analyses indicated that increased LIFr expression was an independent prognostic marker for primary melanoma (P = 0.036). LIFr knockdown inhibited melanoma cell migration in wound healing assays and reduced stress fiber formation. LIFr knockdown correlated with STAT3 suppression, but not YAP, suggesting that LIFr activation might stimulate melanoma cell migration through the STAT3 pathway. Our data indicate that strong LIFr expression identifies potentially highly malignant melanocytic lesions at an early stage and LIFr may be a potential target for the development of early intervention therapeutics.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694846/
_version_	1613517782995959808

High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma

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