Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions?

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Tumor cells utilize diverse post-translational modifications to regulate gene expression.
• Emerging research highlights the role of extracellular cytoplasmic proteins in modulating cell surface receptor function.
• Proteins such as epimorphin, FGF1, FGF2, PLK1, and Ku80 exhibit moonlighting functions in oncogenesis and inflammation.

Purpose of the Study:

• To review the molecular mechanisms of unconventional cytoplasmic protein export.
• To focus on the role of RHAMM (Receptor Activity Modifying Protein) in cancer.
• To explore RHAMM's interactions and impact on tumor progression and therapeutic potential.

Main Methods:

• Review of existing literature on unconventional protein export.
• Analysis of RHAMM's intracellular and extracellular functions.
• Examination of RHAMM's interactions with BRCA1, BARD1, and CD44.

Main Results:

• Intracellular RHAMM interacts with BRCA1 and BARD1, potentially mitigating its role in genomic instability.
• Extracellular RHAMM enhances CD44 surface display and CD44-mediated signaling via ERK1/2.
• RHAMM's export influences tumor progression by modifying tumor suppressor and promoter activities.

Conclusions:

• Unconventional protein export is a novel mechanism influencing cancer progression.
• RHAMM's dual intracellular and extracellular roles highlight its significance in oncogenesis.
• Targeting unconventional protein export pathways, including RHAMM, may offer new therapeutic strategies.