GPR168 functions as a tumor suppressor in mouse melanoma by restraining Akt signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• G protein-coupled receptors

Background:

• Malignant melanoma (MM) incidence is rising globally, despite treatment advances.
• G protein-coupled receptor 168 (GPR168), also known as MrgprF, shows low expression in many cancers, including MM.
• Statistical analysis of The Cancer Genome Atlas (TCGA) data confirms GPR168 downregulation in melanoma versus normal melanocytes.

Purpose of the Study:

• To investigate the effects of GPR168 overexpression in MM cells.
• To elucidate the molecular mechanisms underlying GPR168's function in melanoma.
• To explore GPR168's role in melanoma using in vitro and in vivo models.

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) for statistical analysis of GPR168 expression.
• Employed the mouse melanoma B16-F10 cell line for in vitro studies.
• Used a xenograft tumor model to assess GPR168's in vivo effects.
• Conducted mechanistic studies involving the Akt signaling pathway and performed rescue experiments with anti-GPR168 polyclonal antibodies.

Main Results:

• GPR168 overexpression significantly inhibited B16-F10 cell proliferation, migration, and xenograft tumor growth.
• Mechanistic studies revealed GPR168 impacts melanoma progression via the Akt pathway, decreasing p-Akt, p-GSK-3β, β-catenin, Myc, CyclinD1, and CDK4 expression.
• Rescue experiments using anti-GPR168 antibodies restored cell proliferation and migration, validating GPR168's inhibitory role.

Conclusions:

• GPR168 overexpression suppresses proliferation and migration in mouse melanoma cells through the Akt signaling pathway.
• These findings establish GPR168 as a potential novel tumor suppressor in malignant melanoma.
• GPR168 represents a promising therapeutic target for future interventions in MM treatment.