Related Experiment Video

Updated: Jun 1, 2025

A 3D Organotypic Melanoma Spheroid Skin Model
08:49

A 3D Organotypic Melanoma Spheroid Skin Model

Published on: May 18, 2018

15.6K

Role of the androgen receptor in melanoma aggressiveness

Marzia Di Donato1, Costanza Maria Cristiani2, Mariaelena Capone3

  • 1Department of Precision Medicine, University of Campania 'L. Vanvitelli'- Via L. De Crecchio 7, 80138, Naples, Italy.

Cell Death & Disease
|January 21, 2025
PubMed

Insights

Androgen receptor activation promotes melanoma invasiveness and immune evasion by triggering MICA shedding. Blocking the androgen receptor or ADAM10 enhances natural killer cell activity and improves immunotherapy response in melanoma patients.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Malignant melanoma incidence is rising globally, with increasing resistance to novel therapies.
  • Gender disparities exist in melanoma, and the androgen receptor's role is under investigation.
  • Advanced melanoma requires new therapeutic targets and drugs for improved patient outcomes.

Purpose of the Study:

  • To investigate the role of the androgen receptor (AR) in melanoma progression and immune evasion.
  • To identify molecular mechanisms underlying AR-mediated melanoma invasiveness and resistance to natural killer (NK) cell cytotoxicity.
  • To explore the potential of targeting the AR axis for melanoma treatment and improving immunotherapy efficacy.

Main Methods:

  • Utilized experimental approaches to study melanoma cell invasiveness and MICA shedding.
  • Investigated the effect of androgen receptor activation and blockade on melanoma immune escape.
  • Analyzed MICA serum levels in melanoma patients treated with pembrolizumab (anti-PD-1).
  • Assessed the responsiveness of AR-depleted melanoma cells to immunocheckpoint inhibitors.

Main Results:

  • Ligand activation of the androgen receptor promotes melanoma invasiveness and escape from NK cell-mediated killing.
  • Androgen receptor signaling triggers the shedding of MICA, a surface molecule, facilitating immune escape.
  • Blocking ADAM10 or the androgen receptor inhibits androgen-induced MICA shedding and melanoma immune escape.
  • Elevated MICA serum levels correlate with poor outcomes in patients treated with pembrolizumab.
  • Melanoma cells lacking androgen receptor show enhanced sensitivity to immunocheckpoint inhibitors.

Conclusions:

  • The androgen receptor plays a critical role in driving melanoma invasiveness and immune evasion.
  • Androgen receptor signaling, through MICA shedding, contributes to resistance against natural killer cell surveillance.
  • Targeting the androgen receptor axis, including MICA shedding via ADAM10, offers a potential therapeutic strategy.
  • Androgen receptor status may serve as a diagnostic marker, and AR blockers could be repositioned for melanoma treatment, potentially enhancing immunotherapy efficacy.

More Related Videos

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis07:41

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

2.4K
Experimental Metastasis Assay08:28

Experimental Metastasis Assay

Published on: August 24, 2010

20.2K

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...
6.4K
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...
3.7K
Skin Cancer01:30

Skin Cancer

Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
3.1K
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...
4.4K
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
69.3K
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...
6.2K