Prostaglandin D<sub>2</sub>inhibits TGF-β<sub>1</sub>-induced epithelial-to-mesenchymal transition in MDCK cells

Zhang, Aihua; Zheng, Dong; Yang, Tianxin

doi:10.1152/ajprenal.00131.2006

Cited by 60 publications

(53 citation statements)

References 51 publications

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“…MDCK is usually used in EMT study and undergoes typical morphologic changes of EMT, which is induced by TGFb (13,14). These results indicated that TGFb stimulation was induced through a classical change of EMT markers, leading to a significant increase of LASP1 expression.…”

Section: Lasp1 Regulated Pivotal Biologic Processes and Activated Mulmentioning

confidence: 89%

LIM and SH3 Protein 1 Induces TGFβ-Mediated Epithelial–Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression

Wang

Shi

Luo

et al. 2014

Clinical Cancer Research

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Purpose: The expression of LIM and SH3 protein 1 (LASP1) was upregulated in colorectal cancer cases, thereby contributing to the aggressive phenotypes of colorectal cancer cells. However, we still cannot decipher the underlying molecular mechanism associated with colorectal cancer metastasis.Experimental Design: In this study, IHC was performed to investigate the expression of proteins in human colorectal cancer tissues. Western blot analysis was used to assess the LASP1-induced signal pathway. Two-dimensional difference gel electrophoresis was performed to screen LASP1-modulated proteins and uncover the molecular mechanism of LASP1. TGFb was used to induce an epithelial-mesenchymal transition (EMT).Results: LASP1 expression was correlated with the mesenchymal marker vimentin and was inversely correlated with epithelial markers, namely, E-cadherin and b-catenin, in clinical colorectal cancer samples. The gain-and loss-of-function assay showed that LASP1 induces EMT-like phenotypes in vitro and in vivo. S100A4, identified as a LASP1-modulated protein, was upregulated by LASP1. Moreover, it is frequently coexpressed with LASP1 in colorectal cancer. S100A4 was required for EMT, and an increased cell invasiveness of colorectal cancer cell is induced by LASP1. Furthermore, the stimulation of TGFb resulted in an activated Smad pathway that increased the expression of LASP1 and S100A4. The depletion of LASP1 or S100A4 expression inhibited the TGFb signaling pathway. Moreover, it significantly weakened the proinvasive effects of TGFb on colorectal cancer cells.Conclusion: These findings elucidate the central role of LASP1 in the TGFb-mediated EMT process and suggest a potential target for the clinical intervention in patients with advanced colorectal cancer. Clin Cancer Res; 20(22); 5835-47. Ó2014 AACR.

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Section: Lasp1 Regulated Pivotal Biologic Processes and Activated Mulmentioning

confidence: 89%

LIM and SH3 Protein 1 Induces TGFβ-Mediated Epithelial–Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression

Wang

Shi

Luo

et al. 2014

Clinical Cancer Research

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“…Zhang et al 32 demonstrate that PGD 2 inhibits TGFb1-induced epithelial to mesenchymal transition (EMT) in MDCK cells, and EMT is a major event in the pathogenesis of renal tubulointerstitial fibrosis. However, we could not see any difference in the expression levels of cadherin1 and vimentin, hallmarks of EMT, between the kidney of L-PGDS-KO and WT mice at 5 days and 10 days after UUO (Supplemental Figure 4).…”

Section: Discussionmentioning

confidence: 99%

PGD2-CRTH2 Pathway Promotes Tubulointerstitial Fibrosis

Ito

Yan

Nagata

et al. 2012

Journal of the American Society of Nephrology

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Urinary excretion of lipocalin-type PGD 2 synthase (L-PGDS), which converts PG H 2 to PGD 2 , increases in early diabetic nephropathy. In addition, L-PGDS expression in the tubular epithelium increases in adriamycin-induced nephropathy, suggesting that locally produced L-PGDS may promote the development of CKD. In this study, we found that L-PGDS-derived PGD 2 contributes to the progression of renal fibrosis via CRTH2-mediated activation of Th2 lymphocytes. In a mouse model, the tubular epithelium synthesized L-PGDS de novo after unilateral ureteral obstruction (UUO). L-PGDS-knockout mice and CRTH2-knockout mice both exhibited less renal fibrosis, reduced infiltration of Th2 lymphocytes into the cortex, and decreased production of the Th2 cytokines IL-4 and IL-13. Furthermore, oral administration of a CRTH2 antagonist, beginning 3 days after UUO, suppressed the progression of renal fibrosis. Ablation of IL-4 and IL-13 also ameliorated renal fibrosis in the UUO kidney. Taken together, these data suggest that blocking the activation of CRTH2 by PGD 2 might be a strategy to slow the progression of renal fibrosis in CKD.

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“…MDCK is commonly used in EMT study and can undergo typical morphologic changes of EMT induced by TGF-b (26). MDCK cells appeared spindle-shaped and fibroblastic-like instead of the cobblestone-like phenotype induced by TGF-b.…”

Section: Fmnl2 Is Involved In Tgf-b-induced Emt and Crc Cell Invasionmentioning

confidence: 99%

FMNL2 Enhances Invasion of Colorectal Carcinoma by Inducing Epithelial-Mesenchymal Transition

Zhu

Zeng

et al. 2010

Molecular Cancer Research

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FMNL2 is a member of diaphanous-related formins that control actin-dependent processes such as cell motility and invasion. Its overexpression in metastatic cell lines and tissues of colorectal carcinoma has been associated with aggressive tumor development in our previous study. But its specific role in cancer is largely unknown. Here we report that FMNL2 is involved in epithelial-mesenchymal transition (EMT) maintenance in human colorectal carcinoma cells. A positive correlation between FMNL2 and vimentin expression and an inverse correlation between FMNL2 and E-cadherin expression were found in colorectal carcinoma cell lines and cancer tissues. Specific knockdown of FMNL2 led to an epithelial-state transition, confirmed by the cobblestone-like phenotype, upregulation of E-cadherin, a-catenin, and g-catenin, and downregulation of vimentin, snail, slug. Loss of FMNL2 expression lowered the ability of TGF-b to induce cell invasion and EMT, as shown by morphology and the expression levels. Upregulation of vimentin, slug, snail, downregulation of E-cadherin and activation of receptor-Smad3 phosphorylation were observed in M5 and MDCK cells induced by TGF-b, whereas altered expression of these markers was not obvious in FMNL2-depleting M5 cells. High levels of activation of p-MAPK and p-MEK, but not p-PI3K and p-AKT, were observed in SW480/FMNL2þ cells compared with control cells.Treatment with U0126 could abrogate the activation of p-MAPK and p-MEK, whereas LY294002 treatment had no effect on the PI3K/AKT pathway. In conclusion, these findings identify a novel EMT and tumor promoting function for FMNL2, which is involved in TGF-b-induced EMT and colorectal carcinoma cell invasion via Smad3 effectors, or in collaboration with MAPK/MEK pathway. Mol Cancer Res; 8(12); 1579-90. Ó2010 AACR.

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Prostaglandin D₂inhibits TGF-β₁-induced epithelial-to-mesenchymal transition in MDCK cells

Cited by 60 publications

References 51 publications

LIM and SH3 Protein 1 Induces TGFβ-Mediated Epithelial–Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression

LIM and SH3 Protein 1 Induces TGFβ-Mediated Epithelial–Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression

PGD2-CRTH2 Pathway Promotes Tubulointerstitial Fibrosis

FMNL2 Enhances Invasion of Colorectal Carcinoma by Inducing Epithelial-Mesenchymal Transition

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Prostaglandin D2inhibits TGF-β1-induced epithelial-to-mesenchymal transition in MDCK cells

Cited by 60 publications

References 51 publications

LIM and SH3 Protein 1 Induces TGFβ-Mediated Epithelial–Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression

LIM and SH3 Protein 1 Induces TGFβ-Mediated Epithelial–Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression

PGD2-CRTH2 Pathway Promotes Tubulointerstitial Fibrosis

FMNL2 Enhances Invasion of Colorectal Carcinoma by Inducing Epithelial-Mesenchymal Transition

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Prostaglandin D₂inhibits TGF-β₁-induced epithelial-to-mesenchymal transition in MDCK cells