Related Experiment Video

Updated: Jul 23, 2026

Experimental Metastasis Assay
08:28

Experimental Metastasis Assay

Published on: August 24, 2010

Loss of oncostatin M receptor beta in metastatic melanoma cells

A Lacreusette1, J-M Nguyen, M-C Pandolfino

  • 1INSERM, U601, Groupe de Recherche Cytokines et Récepteurs, Institut de Biologie, Nantes, France.

Oncogene
|August 16, 2006
PubMed

Insights

Metastatic melanoma cells can resist Oncostatin M (OSM) growth inhibition by epigenetically silencing the OSM receptor-beta (OSMRbeta). Reactivating OSMRbeta expression with Trichostatin A restores OSM

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Oncostatin M (OSM), an interleukin-6 (IL-6) type cytokine, inhibits melanoma cell proliferation.
  • Mechanisms of resistance to OSM growth inhibition in metastatic melanoma are not well understood.

Purpose of the Study:

  • Investigate the mechanisms of resistance to OSM growth inhibition in metastatic melanoma.
  • Identify potential therapeutic strategies to overcome OSM resistance.

Main Methods:

  • Analysis of a large panel of metastatic melanoma cell lines for resistance to OSM.
  • Correlation analysis of OSM resistance with resistance to other cytokines (IL-6, IFN-gamma, TNF-alpha).
  • Assessment of OSM receptor-beta (OSMRbeta) subunit expression and its promoter acetylation.
  • Treatment of OSM-resistant cells with histone deacetylase inhibitor Trichostatin A (TSA).
  • Evaluation of signal transducer and activator of transcription 3 (STAT3) activation and downstream effects.

Main Results:

  • OSM resistance correlated with loss of OSMRbeta subunit and reduced histone acetylation in the OSMRbeta promoter.
  • Trichostatin A treatment increased OSMRbeta promoter activity, histone acetylation, and OSMRbeta expression in resistant cells.
  • Restored OSMRbeta expression enabled OSM to activate STAT3 and inhibit melanoma proliferation.
  • Additional defects in OSMRbeta expression/transcription and downstream/parallel to STAT3 activation were observed.

Conclusions:

  • Epigenetic silencing of OSMRbeta is a key mechanism of OSM resistance in metastatic melanoma.
  • Targeting OSMRbeta epigenetic regulation could be a therapeutic strategy to restore OSM sensitivity.
  • OSM plays a role in preventing melanoma progression, and resistance can be overcome by epigenetic modulation.

More Related Videos

A 3D Organotypic Melanoma Spheroid Skin Model08:49

A 3D Organotypic Melanoma Spheroid Skin Model

Published on: May 18, 2018

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...