Oncotarget

Research Papers:

Leptin receptor signaling via Janus kinase 2/Signal transducer and activator of transcription 3 impacts on ovarian cancer cell phenotypes

Janani Kumar, Hao Fang, Daniel R. McCulloch, Tamsyn Crowley and Alister C. Ward _

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Oncotarget. 2017; 8:93530-93540. https://doi.org/10.18632/oncotarget.19873

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Abstract

Janani Kumar1,*, Hao Fang1,*, Daniel R. McCulloch1,2, Tamsyn Crowley1,2 and Alister C. Ward1,2

1School of Medicine, Deakin University, Geelong, Victoria, Australia

2Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia

*These authors have contributed equally to this work

Correspondence to:

Alister C. Ward, email: award@deakin.edu.au

Keywords: ovarian cancer, leptin receptor, JAK2, STAT3, cancer phenotypes

Received: October 28, 2016    Accepted: July 11, 2017    Published: August 03, 2017

ABSTRACT

Ovarian cancer is a leading cause of cancer mortality in women world-wide. Considerable progress has been made to characterize the different subtypes of ovarian cancer, but specific therapies remain limited and prognosis poor. Cytokine signaling via the interleukin-6 receptor (IL-6R) family and related receptors has been implicated in a number of cancers, including those with an ovarian origin. The leptin receptor (LEPR) is structurally related to these receptors and utilizes similar downstream pathways. LEPR has diverse roles in metabolism, appetite and bone formation with obesity linked to both elevated levels of leptin and increased cancer incidence. This study investigated a potential role for LEPR signaling in ovarian cancer. Leptin stimulation led to increased proliferation, survival and migration of LEPR-expressing ovarian cancer cell lines, with the effects shown to be mediated by the downstream Janus kinase 2/Signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. A significant correlation was identified between high co-expression of leptin and LEPR and decreased patient survival. This study collectively suggests that leptin/LEPR signaling via JAK2/STAT3 has the potential to significantly impact on pathogenesis in a subset of ovarian cancer patients who may benefit from strategies that dampen this pathway.


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