HMN 2026: How to Understand the role of the protein PAX3 in cancer development

Paired Box 3 (PAX3) is a protein that plays a critical role in the formation of tissues and organs during embryonic development and can positively (and less frequently, negatively) regulate gene expression. While progress has been made to advance our understanding of this critical and multi-faceted protein, there is still much that is unknown about the mechanisms by which PAX3 controls such a wide array of key cellular functions.

In a new review in the journal Biomolecules, researchers report that PAX3 is essential for the development of nerves, muscles, and melanocytes in embryos, and also plays a role in maintaining adult tissues in stem cells. Additionally, in some cancers, such as some muscle tumors and melanoma, researchers found that PAX3 is present at abnormally high levels and promotes tumor progression.

“PAX3 is a dynamic and multi-faceted transcription factor that plays numerous roles in both development and disease, underscoring the importance of improving our understanding of this vital factor,” says corresponding author Deborah Lang, Ph.D., associate professor of dermatology at Boston University Chobanian & Avedisian School of Medicine.

To better understand this protein, the researchers performed an overview of the literature and recent findings. They reviewed the PAX3 structure and post-translational modifications, the regulation of PAX3 expression, PAX3’s known transcriptional targets and binding partners in normal states of development and PAX3 in mature tissues. They also studied PAX3’s role in Waardenburg Syndrome, melanoma, alveolar rhabdomyosarcoma (pediatric soft tissue sarcoma), and neuroblastoma.

According to the researchers, the role of PAX3 in normal and pathological cells may give clues to therapies for tissue regeneration or blocking tumor growth. “In stem cells, cells often recycle pathways that were active during embryonic development, and these pathways may become subverted in cancers. As a potential therapeutic, PAX3 function may be promoted in regenerating cells for stem cell therapy, or inhibited when these cells grow out of control such as in cancer,” adds Lang.

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