Oncotarget

Research Papers:

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

Hongwei Guo _, Yabin Cheng, Magdalena Martinka and Kevin McElwee

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Oncotarget. 2015; 6:25484-25498. https://doi.org/10.18632/oncotarget.4688

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Abstract

Hongwei Guo1,2, Yabin Cheng1, Magdalena Martinka3, Kevin McElwee1

1Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada

2Department of Dermatology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China

3Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence to:

Hongwei Guo, e-mail: [email protected]

Keywords: LIFr, melanoma, biomarker, cell migration

Received: January 21, 2015     Accepted: July 13, 2015     Published: July 25, 2015

ABSTRACT

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.


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