Proteomic analysis of tumor necrosis factor-α resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype

Zhou, Changhua; Nitschke, Ashley; Xiong, Wei; Zhang, Qiang; Tang, Yan; Bloch, Michael J.; Elliott, Steven; Zhu, Yun; Bazzone, Lindsey E.; Yu, David C.; Weldon, Christopher B.; Schiff, Rachel; McLachlan, John A.; Beckman, Barbara S.; Wiese, Thomas E.; Nephew, Kenneth P.; Shan, Bin; Burow, Matthew E.; Wang, Guangdi

doi:10.1186/bcr2210

Cited by 100 publications

(101 citation statements)

References 58 publications

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“…EMT is an important biological process of tumor progression. Recent findings suggest that TNF-a induces snail promoter activity and EMT in MCF-7 breast cancer cells, 20 reinforcing the association between inflammation and EMT.…”

Section: Discussionmentioning

confidence: 62%

M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway

Liu

Shi

et al. 2013

Laboratory Investigation

389

290

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M2-polarized tumor-associated macrophages (TAMs) are key regulators of the link between inflammation and cancer. A negative correlation between infiltration intensity of M2-polarized TAMs and prognosis of pancreatic cancer has been reported. Epithelial-mesenchymal transition (EMT) is an important biological process in the progression of primary tumors toward metastasis. Inflammation-induced EMT has been previously shown, therefore, we hypothesized M2-polarized TAMs could induce EMT in pancreatic cancer. Toll-like receptor 4 (TLR4) signaling has an active role in tumor progression during chronic inflammation and the receptor is primarily expressed on macrophages. Activation of TLR4 on M2-polarized TAMs stimulates an increase in the cytokine interleukin-10 (IL-10); consequently, another aim was to investigate the potential role of TLR4/IL-10 signaling in the EMT of pancreatic cancer. Treatment with IL-4 (20 ng/ml) for 24 h successfully induced the polarization of macrophage cell line RAW 264.7 to M2 phenotype, IL-10 high , IL-12 low , and IL-23 low , and high expression of CD204 and CD206. A coculture system allowed investigation of the roles of M2-polarized TAMs and TLR4/IL-10 signaling in the EMT of Panc-1 and BxPC-3 pancreatic cancer cell lines. Our results showed that coculture with M2-polarized TAMs increased fibroblastic morphology, upregulated mesenchymal markers vimentin and snail at the mRNA and protein levels, and increased proliferation, migration, and metalloproteinase (MMP)2 and MMP9 proteolytic activity in pancreatic cancer cells. Simultaneously, coculture with M2-polarized TAMs decreased the expression of the epithelial marker E-cadherin. Coculture with pancreatic cancer cells increased TLR4 mRNA and protein expression in M2-polarized TAMs. Application of TLR4 siRNA and neutralizing antibodies against TLR4 and IL-10 markedly inhibited E-cadherin reduction and the upregulation of snail and vimentin. Furthermore, activation of TLR4 signaling by lipopolysaccharide profoundly increased the EMT of pancreatic cancer cells. In conclusion, M2-polarized TAMs promoted EMT in pancreatic cancer cells partially through TLR4/IL-10 signaling, suggesting novel therapeutic strategies and enhancing our understanding of M2-polarized TAMs. Pancreatic ductal adenocarcinoma is highly malignant and is resistant to chemo-and radiotherapeutics. 1 Recent evidence suggests the inflammatory environment of the tumor is critical for its progression. 2 Tumor-associated macrophages (TAMs) are derived from circulating monocytes, which are highly abundant within the tumor and provide a key link between inflammation and cancer. 3 TAMs develop a phenotype similar to M2-polarized macrophages and respond to recruitment to the tumor microenvironment. 4 Previous studies have commonly associated elevated numbers of TAMs with tumor progression and poor patient outcome. 5 This association is likely linked to the typical presence of M2-polarized TAMs during cancer invasion, 6 however, the exact mechanisms by which these cells influence the pr...

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Section: Discussionmentioning

confidence: 62%

M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway

Liu

Shi

et al. 2013

Laboratory Investigation

389

290

View full text Add to dashboard Cite

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“…The present study mainly focused on the anti-apoptotic mechanisms to discuss the drug tolerance mechanism of breast cancer. Zhou et al (2008) confirmed that breast cancer cell line MCF-7-MEK5 with transfected MEK5 has a stable EMT phenotype, the induced effect of MEK5 is unaffected by carriers and cells with TNF-α tolerance are associated with EMT. Our previous studies found that the expression of FASN, which is a key enzyme of synthetic long chain fatty acids, is significantly upregulated in MCF-7-MEK5.…”

Section: Discussionmentioning

confidence: 57%

“…MCF-7-MEK5 cells have TNF-α tolerance (Zhou et al, 2008). TNF-α is a multifunctional cytokine with biological effects that can cause diseases, such as inflammation, killing or inhibition of tumour cells and proliferation and differentiation of tumour cells, which produces a double-edged sword effect.…”

Section: Mechanism Of Fatty Acid Synthase In Drug Tolerance Related Tmentioning

confidence: 99%

“…In the EMT process of MCF-7-MEK5 in breast cancer cells, E-cadherin expression significantly decreases (Zhou et al, 2008). E-cadherin is a class of Ca 2+ -dependent transmembrane adhesion receptors with homogeneous affinity, and adheres among epidermal cells as a marker molecule.…”

Section: Mechanism Of Fatty Acid Synthase In Drug Tolerance Related Tmentioning

confidence: 99%

“…They also found that knockdown of DUSP4 reverses EMT in MCF-7/ADR cells (adriamycinresistant), and increases the chemosensitivity of MCF-7/ ADR cells to doxorubicin (Lin et al, 2013). Zhou et al (2008) found that the overexpression of MEK5 induces EMT and tumour necrosis factor-α (TNF-α) tolerance in MCF-7 cells. Thus, studying the mechanism for drug resistance in EMT cells will benefit tumour treatment.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanism of Fatty Acid Synthase in Drug Tolerance Related to Epithelial-mesenchymal Transition of Breast Cancer

Li¹,

Xue²,

Zhou³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Highly selective removal of organic dyes from aqueous solutions with chitin beads entrapping rectorite

Shi

et al. 2014

J of Applied Polymer Sci

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By blending chitin with rectorite and organic rectorite in an 8 wt % NaOH/4 wt % urea aqueous solution, we successfully fabricated millimeter‐scale chitin/rectorite composite beads (BCRs) and chitin/organic rectorite beads (BCO), respectively, via an optimal dropping technology. The adsorption of the organic dyes on the BCRs and BCOs were investigated to evaluate the selective removal of methylene blue (MB) and methyl orange (MO) of different charges. Adsorption kinetics experiments were carried out, and the data fit a pseudo‐second‐order equation well. The results reveal that the BCR and BCO sorbents efficiently and selectively adsorbed MO and MB, respectively, from wastewater. The adsorption capacity (Qe) and removed percentage of MB by BCR were 0.1978 mg/g and 98.90%. The Qe and R values of MO by BCO were 0.3988 mg/g and 99.70%. Therefore, in this study, we dealt with the development of a clean and safe process for water pollution remediation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40905.

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Proteomic analysis of tumor necrosis factor-α resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype

Cited by 100 publications

References 58 publications

M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway

M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway

Mechanism of Fatty Acid Synthase in Drug Tolerance Related to Epithelial-mesenchymal Transition of Breast Cancer

Highly selective removal of organic dyes from aqueous solutions with chitin beads entrapping rectorite

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