scholarly journals Targeting growth hormone receptor in human melanoma cells attenuates tumor progression and epithelial mesenchymal transition via suppression of multiple oncogenic pathways

Oncotarget ◽  
2017 ◽  
Vol 8 (13) ◽  
pp. 21579-21598 ◽  
Author(s):  
Reetobrata Basu ◽  
Shiyong Wu ◽  
John J. Kopchick
Keyword(s):  
Growth Hormone ◽  
Tumor Progression ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Epithelial Mesenchymal Transition ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Mesenchymal Transition ◽  
Human Melanoma Cells ◽  
Oncogenic Pathways

scholarly journals Effects of Growth Hormone in Human Melanoma Drug Resistance

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1016-A1016
Author(s):  
Pranay Arora ◽  
Reetobrata Basu ◽  
John Joseph Kopchick
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Receptor ◽  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Mouse Tumor ◽  
Gh Treatment ◽  
Mesenchymal Transition

Abstract Melanoma, an extremely drug resistant form of cancer, displays elevated levels of growth hormone (GH) and growth hormone receptor (GHR) expression. We have described a GH dependent mechanism of chemoresistance in melanoma through a series of earlier studies. In GHR overexpressing human melanoma, GH action drives active drug efflux and phenotype switching by upregulating ATP-binding cassette transporters (ABC-transporters) and epithelial-to-mesenchymal transition (EMT) markers. Inhibition of GHR activation reverses these effects, increases drug retention, and sensitizes the melanoma cells to chemotherapy. GH action in melanoma also appears to drive drug sequestration in melanosomes as we present here. GH action was found to modulate the levels of melanocyte-inducing transcription factor (MITF), the master regulator of melanosome synthesis and melanoma. Additionally, MITF target gene levels and drug sequestering ABC transporter expression were also elevated by GH treatment in vitro and in vivo in mouse tumor xenografts. This was corroborated by in silico analyses of tumor databases. Furthermore, we observed a dose dependent increase in tyrosinase activity and melanogenesis in human melanoma cells with GH, in the presence of chemotherapy, which was suppressed by siRNA mediated GHR inhibition. Thus, we describe an array of molecular mechanisms by which GH drives chemoresistance in melanoma. Therefore, GHR inhibition combined with chemotherapy should lead to better tumor clearance and improve overall survival.

Capn4 promotes epithelial-mesenchymal transition in human melanoma cells through activation of the Wnt/β-catenin pathway

2016 ◽  
Vol 37 (1) ◽  
pp. 379-387 ◽  
Author(s):  
Enwen Wang ◽  
Donglin Wang ◽  
Bing Li ◽  
Huiwen Ma ◽  
Chunmei Wang ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Mesenchymal Transition ◽  
Human Melanoma Cells

scholarly journals CD63 Tetraspanin Is a Negative Driver of Epithelial-to-Mesenchymal Transition in Human Melanoma Cells

2014 ◽  
Vol 134 (12) ◽  
pp. 2947-2956 ◽  
Author(s):  
Antonella Lupia ◽  
Silvia Peppicelli ◽  
Ewa Witort ◽  
Francesca Bianchini ◽  
Vinicio Carloni ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Mesenchymal Transition ◽  
Human Melanoma Cells
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