ATAD2 (ATPase Family AAA Domain Containing 2)

As revealed by GSEA analysis, the gene set related to spermatid development was downregulated, while gene sets related to chromatin binding and positive and negative DNA-templated transcription were upregulated. In conclusion, our results indicate that ATAD2 contributes to meiotic progression and participates in spermiogenesis by regulating RNA transcription in spermatids.

The in vivo and in vitro experiments showed an important role of GATAD2B in OC growth and metastasis, as confirmed by the inhibited tumor growth and the enhanced M1 macrophage infiltration.GATAD2B m6A methylation mediated by METTL3 can promote malignant progress. And GATAD2B can promote immune escape by MYC/CD47 pathway in OC, providing a promising anti-OC therapeutic target.

The ferroptosis inducer erastin also inhibits melanoma growth. Combining the ATAD2 inhibitor BAY-850 with the MEK inhibitor trametinib potently suppresses melanoma growth. Our study identifies ATAD2 as a key driver of melanoma and provides a rationale for targeting ATAD2 in conjunction with the MAPK pathway to treat melanoma.

Notably, the expression levels of these genes were found to be positively correlated, with patients exhibiting high levels of these genes tending to have poorer prognoses. These findings demonstrate that ATAD2 plays a pivotal role in the malignant progression of glioma and synergizes with E2F1 to promote PDK1 expression, suggesting its potential as a therapeutic target for glioma.

Furthermore, we examine the emerging roles of ATAD2 in mediating resistance to cancer therapies, underscoring its potential as a target for overcoming drug resistance. By integrating structural insights, mechanistic studies, drug discovery efforts, and the challenges of developing ATAD2-targeted cancer therapies, this review emphasizes the need for further research to optimize ATAD2 inhibition strategies and explore its full therapeutic potential in oncology.

ATAD2 is a critical biomarker for poor prognosis and treatment response across a wide range of cancers. Its ability to predict therapeutic responses, particularly for immunotherapy, targeted therapy, and chemotherapy, underscores its clinical significance. Further experimental studies and clinical trials are needed to explore ATAD2's role in cancer progression and its involvement in therapeutic resistance mechanisms.

Additionally, we included progress, including potential monoclonal antibodies, RNA-based therapies, and small chemical inhibitors, in the review. Therefore, we guarantee this study will provide researchers with new opportunities and directions for cancer therapeutics.

Lastly, we show that overexpression of wild-type GATAD2B, but not the mutant lacking C-terminal O-GlcNAc sites, promotes mammosphere formation, expression of CSCs factors and drug resistance. Together, we identify a key role of GATAD2B and ITCH in regulating CSCs in breast cancer and GATAD2B O-GlcNAcylation as a mechanism regulating breast cancer stem-like populations and promoting chemoresistance.

Using functional studies on mouse bone metastatic cell lines and innovative organ-on-a-chip bone invasion assays, we establish a functional role for ATAD2 inhibition in diminishing prostate cancer metastasis and growth in bone. Implications: Our study highlights ATAD2 as a driver of prostate cancer progression and metastasis and suggests it may constitute a promising novel therapeutic target.

Our findings highlight the potential of targeting the ATAD2 YSDDDVPSV immunopeptide for SCLC immunotherapy, thereby offering a promising avenue for the development of adoptive T cell therapies to effectively treat ASCL1-positive or NEUROD1-positive SCLC carrying HLA-A∗02:01.

Despite achieving initial remission with venetoclax-based therapy and allo-HSCT, the patient relapsed and died. We propose that the GATAD2B::MTCP1 fusion upregulates MTCP1 expression rather than generating a fusion protein, thereby contributing to transformation and relapse in AML. Further investigations are needed to elucidate the precise role of this fusion event in myeloid malignancies.

Lastly, the overexpression of ATAD2 and TWIST1 enhances cell proliferation, emphasizing their role in colorectal carcinoma progression through MYC activation. Together, these results suggest that ATAD2 is a crucial factor in TWIST1-dependent MYC gene activation, resulting in an active ATAD2-TWIST1-MYC axis that contributes to colon cancer cell proliferation.