RGD Reference Report - DAMTC regulates cytoskeletal reorganization and cell motility in human lung adenocarcinoma cell line: an integrated proteomics and transcriptomics approach. - Rat Genome Database

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

Authors: Goel, A  Chhabra, R  Ahmad, S  Prasad, A K  Parmar, V S  Ghosh, B  Saini, N 
Citation: Goel A, etal., Cell Death Dis. 2012 Oct 11;3(10):e402. doi: 10.1038/cddis.2012.141.
RGD ID: 155791641
Pubmed: PMID:23059821   (View Abstract at PubMed)
PMCID: PMC3481129   (View Article at PubMed Central)
DOI: DOI:10.1038/cddis.2012.141   (Journal Full-text)

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 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 (RhoGDIα (Rho GDP dissociation inhibitor-α, 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 RhoGDIα. 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.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
7,8-diacetoxy-4-methylcoumarin decreases expression EXP 155791641DAMTC decreases expression of RAC1 protein in non-small cell lung cancer cellsRGD 
7,8-diacetoxy-4-methylcoumarin decreases expression ISORAC1 (Homo sapiens)155791641; 155791641DAMTC decreases expression of RAC1 protein in non-small cell lung cancer cellsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Rac1  (Rac family small GTPase 1)

Genes (Mus musculus)
Rac1  (Rac family small GTPase 1)

Genes (Homo sapiens)
RAC1  (Rac family small GTPase 1)


Additional Information