ReferenceID 1071
Abscisic acid regulates dormancy of prostate cancer disseminated tumor cells in the bone marrow
Neoplasia
Prostate cancer (PCa) commonly metastasizes to the bone where the cells frequently undergo dormancy. The escape of disseminated tumor cells from cellular dormancy is a major cause of recurrence in marrow. Abscisic acid (
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Record Fields
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- Reference Id
- 1071
- Evidence Id
- 17661
- Core Evidence Id
- 17661
- Source Reference Id
- 2130
- Herb2 Reference Id
- HBREF002927
- Subject Paper Key
- HBIN014230_33296752
- Pubmed Id
- 33296752
- Doi
- 10.1016/j.neo.2020.11.009
- Paper Title
- Abscisic acid regulates dormancy of prostate cancer disseminated tumor cells in the bone marrow
- Paper Abstract
- Prostate cancer (PCa) commonly metastasizes to the bone where the cells frequently undergo dormancy. The escape of disseminated tumor cells from cellular dormancy is a major cause of recurrence in marrow. Abscisic acid (ABA), a phytohormone, is known to regulate dormancy of plant seeds and to regulate other stress responses in plants. Recently, ABA was found to be synthesized by mammals cells and has been linked to human disease. Yet the role of ABA in regulating tumor dormancy or reactivation is unknown. We found that ABA is produced by human marrow cells, and exogenous ABA inhibits PCa cell proliferation while increasing the expression of p27, p21, and p16 and decreasing the expression of the proliferation marker, Ki67. Further, ABA significantly increased the percentage of PCa cells in the G0 phase of the cell cycle as well as the duration the cells were arrested in G0. We found that ABA regulates an increase of PPARgamma receptor expression and suppressed phosphorylation of mTOR/p70S6K signaling and resulting in the induction of the cellular dormancy. We then confirmed that ABA regulates G0 cell cycle arrest through PPARgamma receptor signaling in vitro and under co-culture conditions with osteoblasts. Finally, we demonstrate that ABA regulates PCa dormancy in vivo following intratibial injection in an animal model. Together these data suggest that the ABA and PPARgamma signaling pathways contribute to the establishment of PCa cellular dormancy in the bone marrow microenvironment. These findings may suggest critical pathways for targeting metastatic disease.
- Journal
- Neoplasia
- Publish Year
- 2021
- Experiment Subject
- human
- Experiment Type
- Cell Experiment
- Phenotype Related
- Tumor; Metastatic Disease; Pca; Prostate Cancer
- Paper Title Cn
- Paper Title En
- Abscisic acid regulates dormancy of prostate cancer disseminated tumor cells in the bone marrow
- Bilingual Status
- semi_complete