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• W4306175344 abstract "Abstract In recent years, significant progress has been made to the use‐case of small peptides because of their diversified edifice and hence their versatile application scope in cancer therapy. Here we identify the heterochiral dipeptide H‐ D Phe‐ L Phe‐OH (F1) as a potent inducer of the metastatic suppressor NM23H1. We divulge the effect of F1 on the major EMT/metastasis‐associated genes and the implications on the invasion and migration ability of cancer cells. The anti‐invasive potential of F1 was directly correlated with NM23H1 expression. Mechanistically, F1 treatment elevated p53 levels as validated by localization and transcriptional studies. In the NM23H1 knockdown condition, F1 failed to induce any p53 expression/nuclear localization, indicating that the upregulation in p53 expression by F1 is NM23H1 dependent. We also demonstrate how the antimetastatic potential of F1 is primarily mediated through NM23H1 irrespective of the p53 status of the cell. However, both NM23H1 and a functional p53 protein in conjunction govern the apoptotic and cytostatic potential of F1. Coimmunoprecipitation studies unraveled the augmentation of the p53 and NM23H1 interaction in p53 wild‐type cells. However, in p53 mutated cells, no such enrichment was evidenced. We employed mouse isogenic cell lines (4T‐1 and 4T‐1 p53) to determine the in vivo efficacy of F1 (spontaneous and experimental models). Decreased tumor volume in the cohort injected with 4T‐1 p53 cells demonstrated that while the antimetastatic potential of F1 was reliant on NM23H1, p53 activation was required for ablation of primary tumor burden. Our findings unravel that F1 treatment induces significant abrogation of the migration, invasion and metastatic potential of both p53 wild‐type and p53 deficient cancers mediated through NM23H1." @default.
• W4306175344 created "2022-10-14" @default.
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• W4306175344 date "2022-10-14" @default.
• W4306175344 modified "2023-09-26" @default.
• W4306175344 title "Heterochiral dipeptide <scp>d</scp>‐phenylalanyl‐<scp>l</scp>‐phenylalanine (H‐^DPhe‐^LPhe‐OH) as a potential inducer of metastatic suppressor NM23H1 in p53 wild‐type and mutant cells" @default.
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• W4306175344 doi "https://doi.org/10.1002/mc.23465" @default.
• W4306175344 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36239557" @default.
• W4306175344 hasPublicationYear "2022" @default.
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