Hydroxycamptothecin Impedes the Mesenchymal Stem Cells (MSCs)-Triggered Migrative Features of Breast Cancer Cells via Suppressing the Protein Kinase B/Mitogen-Activated Protein Kinase (AKT/MAPK) Activation in Bone Marrowmesenchymal Stem Cells

The current study aimed to dissect the impacts and mechanisms of hydroxycamptothecin on breast cancer. Collect conditioned medium from MSCs cells to apply it into the co-culture system of breast cancer cells, which were pre-treated with hydroxycamptothecin. The cell counting kit was employed to measure the proliferation potential of cells, while the phosphorylation degrees of AKT/MAPKrelated proteins were examined via Western blotting. Then the cellular migration was test by transwell. Finally, the transcriptional and translational levels of IL-6 and RANTES in cells were detected by real-time PCR and enzyme-linked immunosorbent assay. HC could remarkably influence the interplay between MSC and breast malignant cells, reduce the MSC-activated migrative behavior of breast malignant cells and impede the capability of MSC to maintain the migration of cancer cells. RANTES and IL-6 exerted a synergistic induction in the migrative feature of breast cancer cells. HC could retard the migrating activities of breast cancer cells via diminishing the RANTES and IL-6 levels. Hydroxycamptothecin could impede the proliferative and migrative activities of MSC, of which the impediment was accompanied by an inhibitory impact on the secretory production of two growth factors IL-6 and RANTES from MSC, thereby enhancing the migration of breast malignant cells.

Mitogen-Activated Protein Kinase 4-Regulated Metabolic Networks

Mitogen-activated protein kinase 4 (MPK4) was first identified as a negative regulator of systemic acquired resistance. It is also an important kinase involved in many other biological processes in plants, including cytokinesis, reproduction, and photosynthesis. Arabidopsis thaliana mpk4 mutant is dwarf and sterile. Previous omics studies including genomics, transcriptomics, and proteomics have revealed new functions of MPK4 in different biological processes. However, due to challenges in metabolomics, no study has touched upon the metabolomic profiles of the mpk4 mutant. What metabolites and metabolic pathways are potentially regulated by MPK4 are not known. Metabolites are crucial components of plants, and they play important roles in plant growth and development, signaling, and defense. Here we used targeted and untargeted metabolomics to profile metabolites in the wild type and the mpk4 mutant. We found that in addition to the jasmonic acid and salicylic acid pathways, MPK4 is involved in polyamine synthesis and photosynthesis. In addition, we also conducted label-free proteomics of the two genotypes. The integration of metabolomics and proteomics data allows for an insight into the metabolomic networks that are potentially regulated by MPK4.