Cross-regulation between protein L-isoaspartyl O-methyltransferase and ERK in epithelial mesenchymal transition of MDA-MB-231 cells

Aim： Protein L-isoaspartyl O-methyltransferase （PIMT） regulates cell adhesion in various cancer cell lines through activation of integrin av and the PI3K pathway. The epithelial mesenchymal transition （EMT） enables epithelial cells to acquire the characteristics of mesenchymal cells, and to allow th...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2011-09, Vol.32 (9), p.1165-1172
Main Authors: Ryu, Jiyeon, Song, Jihyeok, Heo, Jieun, Jung, Yongwoo, Lee, Sang-Jin, Hong, Sungyoul, Cho, Jae Youl
Format: Article
Language:English
Subjects:
Breast Neoplasms - enzymology
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Line, Tumor
Epithelial-Mesenchymal Transition
ERK
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
MDA
Organic Cation Transport Proteins - genetics
Original
PD98059
Protein D-Aspartate-L-Isoaspartate Methyltransferase - genetics
Protein D-Aspartate-L-Isoaspartate Methyltransferase - metabolism
Transforming Growth Factor beta - metabolism
Tumor Necrosis Factor-alpha - metabolism
上皮细胞
细胞粘附
蛋白质
转化
间质细胞
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Summary:Aim： Protein L-isoaspartyl O-methyltransferase （PIMT） regulates cell adhesion in various cancer cell lines through activation of integrin av and the PI3K pathway. The epithelial mesenchymal transition （EMT） enables epithelial cells to acquire the characteristics of mesenchymal cells, and to allow them to migrate for metastasis. Here, we examined the relationship between PIMT and EMT with attached or detached MDA-MB 231 cells. Methods： Human breast cancer cell line MDA-MB-231 cells were maintained in a suspension on poly-HEMA in the presence or absence of PIMT siRNA or ERK inhibitor PD98059. The mRNAs and proteins were analyzed using RT-PCR and immunoblotting, respectively. Results： During cellular incubation under detached conditions, PIMT, integrin av and EMT proteins, such as Snail, Slug and matrix met- alloproteinase 2 （MMP-2）, were significantly increased in correlation with the phosphorylation of ERK1/2. The ERK inhibitor PD98059 （25 pmol/L） strongly suppressed the expression of the proteins and PIMT. Interestingly, PIMT siRNA blocked the phosphorylation of ERK and the expression of the EMT proteins. Additionally, PIMT and ERK phosphorylation were both co-activated by treatment with TGF-β （10 ng/mL） and TNF-α （10 ng/mL）. Conclusion： A tight cross-regulation exists between ERK and PIMT in regards to their activation and expression during the EMT.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2011.94