Deciphering deubiquitinating enzyme Ataxin-3 as an emerging target for cancer intervention

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• Ataxin-3 (ATXN3) is a deubiquitinating enzyme primarily known for its association with Machado-Joseph disease.
• Emerging research highlights ATXN3's involvement in crucial cancer-related cellular processes, including DNA repair and genome integrity.

Purpose of the Study:

• To synthesize current knowledge on the structural features, physiological functions, and oncogenic mechanisms of ATXN3.
• To evaluate the therapeutic potential and biomarker utility of ATXN3 in oncology.
• To consolidate research on ATXN3's role in cancer, particularly its influence on immune evasion and the tumor microenvironment.

Main Methods:

• This narrative review consolidates findings from diverse preclinical and clinical studies.
• Analysis of ATXN3's structural characteristics and functional roles in cancer pathogenesis.
• Evaluation of signaling pathways (e.g., PI3K/Akt, Hippo/YAP, TGF-β) modulated by ATXN3 in cancer.

Main Results:

• ATXN3 overexpression is observed in various cancers (gastric, breast, lung, etc.) and correlates with aggressive phenotypes and poor prognosis.
• ATXN3 influences cancer progression by regulating proliferation, metastasis, apoptosis resistance, and immune evasion.
• Recent findings implicate ATXN3 in modulating immune checkpoints and tumor microenvironment remodeling.

Conclusions:

• ATXN3 plays a multifaceted role in cancer pathogenesis, extending beyond its known neurodegenerative functions.
• ATXN3 represents a promising, yet underexplored, therapeutic target and potential biomarker in precision oncology.
• Further research into ATXN3 is crucial for developing novel cancer treatment strategies.