A novel Nilotinib derivative N-12 inhibits the proliferation and migration of colon cancer cells through the EMT signaling pathway
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ABSTRACT:
PROVIDER: PRJNA1151662 | ENA |
REPOSITORIES: ENA
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Project description:Colon cancer ranks among the prevalent malignancies globally, and its proclivity for metastasis significantly contributes to the adverse prognostic outcomes observed in patients. The epithelial-mesenchymal transition (EMT) represents a critical biological process through which tumor cells gain migratory and invasive capabilities. Nilotinib is a selective inhibitor of tyrosine kinases, commonly utilized in the treatment of chronic myeloid leukemia (CML). Prior investigations have demonstrated that the Nilotinib derivative, N-12, exhibits significant antitumor properties. The objective of this study is to elucidate the inhibitory effects of N-12 on the progression of EMT in colon cancer cells. So, the human colon cancer cell line HCT116 was selected for experimentation. Initially, assessments of cell proliferation, migration and invasion were conducted utilizing MTT, colony formation, Edu and Transwell assays. Subsequently, the chick embryo chorioallantoic membrane model was employed to evaluate tumor size and its impact on angiogenesis in vivo. Thereafter, HCT116 cells treated with N-12 underwent RNA sequencing for analysis. Finally, the expression levels of EMT markers in colon cancer cells were determined by Western blot analysis. The results showed that N-12 significantly curtails the proliferation, migration, and invasion of colon cancer cells, and concurrently impedes tumor growth in vivo by influencing angiogenesis within the chick embryo chorioallantoic membrane. Furthermore, RNA sequencing and Western blot analyses have elucidated that the antitumor efficacy of N-12 is attributable to the inhibition of the EMT signaling pathway. These results underscore the therapeutic potential of N-12 in the management of colon cancer and delineate its mechanism of action.
2024-09-20 | GSE275553 | GEO
Project description:Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies worldwide. The epithelial-mesenchymal transition (EMT) plays a critical role in tumor invasion and metastasis. Piperine, a natural alkaloid, has demonstrated antitumor activity; however, its low bioavailability limits clinical application. HJJ_3_5, a novel piperine derivative synthesized and validated by our research group, exhibits potent antitumor effects against colorectal cancer cells. In addition to its strong cytotoxicity, HJJ_3_5 disrupts key metastatic processes, including DNA replication, cell migration, invasion, and adhesion, showcasing its multifaceted mechanism of action. In vivo, HJJ_3_5 shows significant efficacy in the CAM model, effectively inhibiting tumor growth and angiogenesis, underscoring its potential as a powerful anti-cancer agent. At the molecular level, comprehensive transcriptomic analysis reveals that HJJ_3_5 significantly downregulates the EMT pathway. Notably, machine learning algorithms identify six core EMT-related genes (COL12A1, PJA2, VCAN, MEF2C, DPYD, and DDR2) as pivotal drivers of cancer progression, with their expression strongly associated with poor clinical outcomes. Single-cell RNA sequencing further reveals that these genes are predominantly expressed in fibroblasts and myofibroblasts, key players in the EMT process and metastasis. These findings position HJJ_3_5 as a promising therapeutic candidate, offering a targeted and potent approach to halting the relentless progression of colorectal cancer.
2024-08-23 | GSE275190 | GEO
Project description:Purpose: To identify differntially expressed transcripts in TP-0903 treated embryos that impair cranila NC EMT and cell migration in zebrafish embryos Methods: zebrafish embryos treated at 13 hpf with 5-7uM TP-0903 and DMSO for 1-, 4- and 8-hrs at 28°C. 35 embryos were collected for each treatment. Results: TP-0903 increases expression of several retinoic acid target genes including genes from within the retinoid pathway Conclusions: TP-0903 causes a direct increase in RA signaling that impairs cranial NC EMT and cell migration in zebrafihs embryos mRNA profiles of zebrafish embryos treated with TP-0903 and DMSO were generated by RNA-Seq, in quadruplicates, using Illumina Hi Seq
2016-02-18 | E-GEOD-72322 | biostudies-arrayexpress
Project description:Purpose: To identify differntially expressed transcripts in TP-0903 treated embryos that impair cranila NC EMT and cell migration in zebrafish embryos Methods: zebrafish embryos treated at 13 hpf with 5-7uM TP-0903 and DMSO for 1-, 4- and 8-hrs at 28°C. 35 embryos were collected for each treatment. Results: TP-0903 increases expression of several retinoic acid target genes including genes from within the retinoid pathway Conclusions: TP-0903 causes a direct increase in RA signaling that impairs cranial NC EMT and cell migration in zebrafihs embryos
2016-02-18 | GSE72322 | GEO
Project description:Tumors and tumor surrounding tissues produce multiple growth factors that influence tumor cell behavior via different signal transduction pathways. Growth factors like transforming growth factor beta (TGFβ) and epidermal growth factor (EGF) were shown to induce proliferation, migration and invasion in different cell models. Both factors are frequently overexpressed in cancer and will often act in combination. Although both factors are being used as rational targets in clinical oncology, similarities and differences of their contributions to cancer cell migration and invasion are not fully understood. Here we compared the impact of TGFβ, EGF and the combination of both factors on A549 cells. Both factors stimulated A549 migration to a similar extent but with a different kinetic and the combination had an additive effect. While EGF-induced migration depended on activation of the mitogen-activated protein kinase (MAPK) pathway, this pathway was dispensable for TGFβ-induced migration despite a strong activation by TGFβ. Proteome analysis revealed an overlap in expression patterns of migration-related proteins and associated gene ontology (GO) terms by TGFβ and EGF but only TGFβ induced the expression of epithelial to mesenchymal transition (EMT)-related proteins like matrix metalloproteinase 2 (MMP2). EGF in contrast, made no major contribution to EMT marker expression on either the protein or the transcript level. In line with these expression patterns, EGF was unable to increase invasion of A549 cells on its own and failed to enhance TGFβ-induced invasion. Overall, these data suggest that TGFβ and EGF may partly compensate each other for stimulation of cell migration but abrogation of TGFβ signaling may be more suitable for antagonizing invasion.
2021-04-08 | PXD023024 | Pride
Project description:We have identified the transcription factor forkhead box protein F2 (Foxf2) to be upregulated in its expression during the EMT process and studied its functional contribution to EMT by siRNA-mediated knockdown in NMuMG cells treated for 4 days with TGFbeta followed by mRNA-sequencing. Our analysis revealed a dual role of Foxf2 during TGFbeta-induced EMT in promoting apoptosis while inducing cell junction breakdown and migration.
2018-10-09 | GSE112796 | GEO
Project description:Resistant cells were generated by stepwise exposure to increasing concentrations of imatinib or nilotinib to establish 0.5 and 2 µM imatinib and 0.1 µM nilotinib resistant cells. This procedure was performed twice independently to establish biological replicates of TKI resistance. We analyzed genome-wide methylation to investigate changes in methylation during the development of TKI resistance.
2022-05-21 | GSE203443 | GEO
Project description:The potential risk of P2Y12 antagonists for cancer treatment is controversial. Here we show that PSB 0739, a P2Y12 antagonist inhibits human cervical cancer cells (Hela and SiHa) migration without modifying cell proliferation. We identify that the co-acetylation and lactylation of epithelial-mesenchymal transition (EMT)-related protein NCL, MYH9, CTTN, S100A6, and ALDOA revealed by proteomic analysis of posttranslational modifications (PTM), are responsible for the PSB0739-induced migration inhibition in human cervical cancer cells. Our data suggest that as one of P2Y12 antagonists, PSB 0739 has no risk in cervical cancer cell migration. The co-modification of acetylation and lactylation of EMT-associated proteins would be novel promising targets to develop new drug for cancer cell migration beyond contributing the potential mechanism of the use of PSB0379 in human cervical cancer cells.
2023-04-06 | PXD041371 |
Project description:miRNA analysis of breast epithelial cell line with stem cell properties before and after undergoing endothelial induced epithelial to mesenchymal transition (EMT). miRNA expression anlysis was done on breast epithelial cells before and after endothelial induced EMT. D492 is a breast epithelial cell line with stem cell properties that undergoes EMT in 3D rBM coculture with endothelial cells. Total RNA was isolated from D492 and D492M (a mesenchymal derivative) at 50% and 90% confluency in monolayer.
2015-07-02 | E-GEOD-60524 | biostudies-arrayexpress
Project description:Resistant cells were generated by stepwise exposure to increasing concentrations of imatinib or nilotinib to establish 0.5 and 2 µM imatinib and 0.1 µM nilotinib resistant cells. This procedure was performed twice independently to establish biological replicates of TKI resistance. We performed microarrays to analyze the changes in gene expression during the development of TKI resistance.
2022-05-21 | GSE203442 | GEO