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DAMTC regulates cytoskeletal reorganization and cell motility in human lung adenocarcinoma cell line: an integrated proteomics and transcriptomics approach.

ABSTRACT: DAMTC (7,8-diacetoxy-4-methylcoumarin) is a thioderivative of 4-methyl coumarin, and previously we have shown that DAMTC is a potent inhibitor of cell growth and an inducer of apoptosis in non-small cell lung cancer (A549) cells. It induces apoptosis through mitochondrial pathway by modulating NF-?B, mitogen-activated protein kinase (MAPK) and p53 pathways. Herein, we explored the genome-wide effects of DAMTC in A549 cells using the concerted approach of transcriptomics and proteomics. In addition to apoptotic pathways, which have been validated earlier, the bioinformatic analysis of microarray data identified small GTPase-mediated signal transduction among the significantly altered biological processes. Interestingly, we observed significant downregulation of some members of the Rho family GTPases in the proteomics data too. Downregulation of Rho GTPases (RhoGDI? (Rho GDP dissociation inhibitor-?, also known as ARHGDIA), Ras homolog family member A, Ras-related C3 botulinum toxin substrate 1 and cell division cycle 42) was validated by western blotting. The Rho protein family is implicated in maintaining the actin filament assembly and cell motility, and we also observed that DAMTC treatment causes actin cytoskeletal reorganization, promotes filopodia formation and inhibits cell motility in A549 cells. The effect of DAMTC treatment on cytoskeleton was reversed after the overexpression of RhoGDI?. In addition, DAMTC augmented the apoptotic effect of etoposide, a proapoptotic chemotherapeutic drug. This elucidation of the mechanism behind DAMTC-induced apoptosis and inhibition of cell motility in A549 cells may make it a potential therapeutic for lung cancer.

SUBMITTER: Goel A

PROVIDER: S-EPMC3481129 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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DAMTC regulates cytoskeletal reorganization and cell motility in human lung adenocarcinoma cell line: an integrated proteomics and transcriptomics approach.

Goel A A Chhabra R R Ahmad S S Prasad A K AK Parmar V S VS Ghosh B B Saini N N

Cell death & disease 20121011

DAMTC (7,8-diacetoxy-4-methylcoumarin) is a thioderivative of 4-methyl coumarin, and previously we have shown that DAMTC is a potent inhibitor of cell growth and an inducer of apoptosis in non-small cell lung cancer (A549) cells. It induces apoptosis through mitochondrial pathway by modulating NF-κB, mitogen-activated protein kinase (MAPK) and p53 pathways. Herein, we explored the genome-wide effects of DAMTC in A549 cells using the concerted approach of transcriptomics and proteomics. In additi ...[more]

PMID: 23059821

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Project description:Lung adenocarcinoma (LUAD) is a highly prevalent and lethal form of lung cancer, comprising approximately half of all cases. It is often diagnosed at advanced stages with brain metastasis (BM), resulting in high mortality rates. Current BM management involves complex interventions and conventional therapies that offer limited survival benefits with neurotoxic side effects. The tumor microenvironment (TME) is a complex system where cancer cells interact with various elements, significantly influencing tumor behavior. Immunotherapies, particularly immune checkpoint inhibitors, target the TME for cancer treatment. Despite their effectiveness, it is crucial to understand metastatic lung cancer and the specific characteristics of the TME, including cell-cell communication mechanisms, to refine treatments. Herein, we investigated the tumor microenvironment of brain metastasis from lung adenocarcinoma (LUAD-BM) and primary tumors across various stages (I, II, III, and IV) using single-cell RNA sequencing (scRNA-seq) from publicly available datasets. Our analysis included exploring the immune and non-immune cell composition and the expression profiles and functions of cell type-specific genes, and investigating the interactions between different cells within the TME. Our results showed that T cells constitute the majority of immune cells present in primary tumors, whereas microglia represent the most dominant immune cell type in BM. Interestingly, microglia exhibit a significant increase in the COX pathway. Moreover, we have shown that microglia primarily interact with oligodendrocytes and endothelial cells. One significant interaction was identified between DLL4 and NOTCH4, which demonstrated a relevant association between endothelial cells and microglia and between microglia and oligodendrocytes. Finally, we observed that several genes within the HLA complex are suppressed in BM tissue. Our study reveals the complex molecular and cellular dynamics of BM-LUAD, providing a path for improved patient outcomes with personalized treatments and immunotherapies.

Dataset Information

DAMTC regulates cytoskeletal reorganization and cell motility in human lung adenocarcinoma cell line: an integrated proteomics and transcriptomics approach.

Publications

DAMTC regulates cytoskeletal reorganization and cell motility in human lung adenocarcinoma cell line: an integrated proteomics and transcriptomics approach.

Similar Datasets

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