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Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Debarshi Banerjee1, Shuobo Boboila1,2, Shunpei Okochi3
1Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.
Cancer Research Communications
|November 28, 2023
Summary
Activating transcription factor 5 (ATF5) drives neuroblastoma metastasis by preventing anoikis, or cell death. Targeting ATF5 with CP-d/n-ATF5 may inhibit metastasis in high-risk neuroblastoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- MYCN-amplified neuroblastoma is aggressive with poor prognosis.
- Activating transcription factor 5 (ATF5) is linked to neural differentiation and cancer survival.
- High ATF5 expression correlates with poor prognosis in stage 4 high-risk neuroblastoma.
Purpose of the Study:
- To investigate the role of ATF5 in neuroblastoma metastasis.
- To elucidate the mechanism by which ATF5 promotes metastasis.
- To evaluate the therapeutic potential of targeting ATF5.
Main Methods:
- Assessed ATF5 expression in neuroblastoma patient samples.
- Utilized in vivo xenograft models to study ATF5's effect on tumor growth and metastasis.
- Investigated ATF5's role in anoikis resistance and its regulation of BMF.
- Tested a dominant-negative ATF5 peptide (CP-d/n-ATF5) for antimetastatic effects.
Main Results:
- ATF5 is highly expressed in high-risk neuroblastoma and associated with poorer prognosis.
- ATF5 promotes neuroblastoma cell metastasis in vivo, reducing xenograft tumor growth and spread to bone marrow and liver.
- ATF5 confers resistance to anoikis by transcriptionally suppressing BMF, enhancing survival of circulating tumor cells.
- CP-d/n-ATF5 peptide treatment inhibited neuroblastoma metastasis and induced anoikis sensitivity.
Conclusions:
- ATF5 is a key promoter of neuroblastoma metastasis.
- ATF5 mediates anoikis resistance in neuroblastoma.
- Targeting ATF5 with CP-d/n-ATF5 is a promising therapeutic strategy against metastatic neuroblastoma.
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