Abscisic acid signaling through LANCL2 and PPARγ induces activation of p38MAPK resulting in dormancy of prostate cancer metastatic cells.

Autor: Parajuli KR; Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, AL 35294, USA., Jung Y; Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA., Taichman RS; Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, AL 35294, USA.
Jazyk: angličtina
Zdroj: Oncology reports [Oncol Rep] 2024 Mar; Vol. 51 (3). Date of Electronic Publication: 2024 Jan 12.
DOI: 10.3892/or.2024.8698
Abstrakt: Prostate cancer (PCa) is one the most common malignancies in men. The high incidence of bone metastasis years after primary therapy suggests that disseminated tumor cells must become dormant, but maintain their ability to proliferate in the bone marrow. Abscisic acid (ABA) is a stress response molecule best known for its regulation of seed germination, stomal opening, root shoot growth and other stress responses in plants. ABA is also synthesized by mammalian cells and has been linked to human disease. The aim of the present study was to examine the role of ABA in regulating tumor dormancy via signaling through lanthionine synthetase C‑like protein 2 (LANCL2) and peroxisome proliferator activated receptor γ (PPARγ) receptors. ABA signaling in human PCa cell lines was studied using targeted gene knockdown (KD), western blotting, quantitative PCR, cell proliferation, migration, invasion and soft agar assays, as well as co‑culture assays with bone marrow stromal cells. The data demonstrated that ABA signaling increased the expression of p21, p27 and p16, while inhibiting viability, migration, invasion and colony size in a reversable manner without toxicity. ABA also induced p38MAPK activation and NR2F1 signaling. Targeted gene KD of LANCL2 and PPARγ abrogated the cellular responses to ABA. Taken together, these data demonstrate that ABA may induce dormancy in PCa cell lines through LANCL2 and PPARγ signaling, and suggest novel targets to manage metastatic PCa growth.
Databáze: MEDLINE