Related Experiment Video

Updated: Jul 4, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

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

Published on: June 7, 2019

Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin

Mei-Yu Hsu1, Sherry A Rovinsky, Chiou-Yan Lai

  • 1Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. mhsu@rics.bwh.harvard.edu

Laboratory Investigation; a Journal of Technical Methods and Pathology
|June 19, 2008
PubMed

Insights

Advanced melanoma cells resist Bone Morphogenetic Protein 7 (BMP7) growth inhibition by upregulating Noggin. This BMP antagonist allows melanoma cells to proliferate, suggesting a mechanism for tumor progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Bone morphogenetic proteins (BMPs), part of the TGF-beta superfamily, regulate crucial cellular functions.
  • BMP7 upregulation correlates with human melanoma progression, yet melanoma cells paradoxically develop resistance.
  • Normal melanocytes are highly susceptible to BMP7, while advanced melanoma cells exhibit resistance.

Purpose of the Study:

  • To investigate the role of BMP antagonists in melanoma cell resistance to BMP7.
  • To test the hypothesis that Noggin protects advanced melanoma cells from BMP7-induced autocrine growth inhibition.

Main Methods:

  • Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) and Western blotting to assess gene and protein expression.
  • Adenoviral gene transfer to overexpress Noggin in melanoma cells.
  • Lentiviral short hairpin RNA (shRNA) to knock down Noggin expression.
  • In vitro assays (anchorage-dependent and -independent growth), 3D skin reconstructs, and in vivo studies in immunodeficient mice.

Main Results:

  • Noggin expression positively correlates with BMP7 resistance in advanced melanoma cells.
  • Noggin overexpression confers a growth advantage to melanoma cells upon BMP7 treatment in vitro, in 3D models, and in vivo.
  • Noggin knockdown restores BMP7 sensitivity and inhibits growth in advanced melanoma cells.

Conclusions:

  • BMP7 acts as an autocrine growth inhibitor in melanocytic cells, similar to TGF-beta.
  • Advanced melanoma cells evade BMP7-induced growth inhibition through aberrant Noggin expression.
  • Targeting Noggin may represent a therapeutic strategy for overcoming BMP7 resistance in melanoma.

More Related Videos

A 3D Organotypic Melanoma Spheroid Skin Model08:49

A 3D Organotypic Melanoma Spheroid Skin Model

Published on: May 18, 2018

Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease06:25

Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease

Published on: March 29, 2024

Related Concept Videos

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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...