Acquisition of epithelial–mesenchymal transition is associated with Skp2 expression in paclitaxel-resistant breast cancer cells

Yang, Qingling; Huang, Jingwen; Wu, Qiong; Cheng, Ying; Zhu, Li; Lu, Xingyue; Chen, S; Chen, C; Wang, Z

doi:10.1038/bjc.2014.136

Cited by 92 publications

(86 citation statements)

References 43 publications

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“…The acquisition of mesenchymal properties has been associated with chemoresistance, including upregulation of TUBB3 and resistance to taxanes (48–50). EMT is characterized by the loss of the epithelial and the gain of the mesenchymal markers, and we observed these alterations in both MCF-7 variants following cabazitaxel selection, indicating that resistance to cabazitaxel is associated with a more aggressive and invasive phenotype.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Resistance to Cabazitaxel

Durán

Wang

Francisco

et al. 2015

Molecular Cancer Therapeutics

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We studied mechanisms of resistance to the novel taxane cabazitaxel in established cellular models of taxane resistance. We also developed cabazitaxel-resistant variants from MCF-7 breast cancer cells by stepwise selection in drug alone (MCF-7/CTAX) or drug plus the transport inhibitor PSC-833 (MCF-7/CTAX-P). Among multidrug resistant (MDR) variants, cabazitaxel was relatively less cross-resistant than paclitaxel and docetaxel (15 vs. 200-fold in MES-SA/Dx5 and 9 vs. 60-fold in MCF-7/TxT50, respectively). MCF-7/TxTP50 cells that were negative for MDR but had 9-fold resistance to paclitaxel were also 9-fold resistant to cabazitaxel. Selection with cabazitaxel alone (MCF-7/CTAX) yielded 33-fold resistance to cabazitaxel, 52-fold resistance to paclitaxel, activation of ABCB1, and 3-fold residual resistance to cabazitaxel with MDR inhibition. The MCF-7/CTAX-P variant did not express ABCB1, nor did it efflux rhodamine-123, BODIPY-labeled paclitaxel, and [3H]-docetaxel. These cells are hypersensitive to depolymerizing agents (vinca alkaloids and colchicine), have reduced baseline levels of stabilized microtubules, and impaired tubulin polymerization in response to taxanes (cabazitaxel or docetaxel) relative to MCF-7 parental cells. Class III β-tubulin (TUBB3) RNA and protein were elevated in both MCF-7/CTAX and MCF-7/CTAX-P. Decreased BRCA1 and altered epithelial-mesenchymal transition (EMT) markers are also associated with cabazitaxel resistance in these MCF-7 variants, and may serve as predictive biomarkers for its activity in the clinical setting. In summary, cabazitaxel resistance mechanisms include MDR (although at a lower level than paclitaxel and docetaxel), and alterations in microtubule dynamicity, as manifested by higher expression of TUBB3, decreased BRCA1, and by the induction of EMT.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of Resistance to Cabazitaxel

Durán

Wang

Francisco

et al. 2015

Molecular Cancer Therapeutics

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“…For example, oxaliplatin-resistant colorectal cancer cells underwent EMT progression [29]. Acquisition of epithelial-mesenchymal transition is associated with Skp2 expression in paclitaxel-resistant breast cancer cells, and tamoxifenresistant MCF7 breast cancer cells showed EMT characteristics with altered b-catenin phosphorylation [30,31]. Similarly, paclitaxel-resistant ovarian cancer cells displayed decreased E-cadherin expression, and increased expression of mesenchymal markers consistent with EMT phenotype [32].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-451 induces epithelial–mesenchymal transition in docetaxel-resistant lung adenocarcinoma cells by targeting proto-oncogene c-Myc

Chen¹,

Huang²,

Zhang³

et al. 2014

European Journal of Cancer

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“…The protein concentrations were measured using the Bio-Rad protein assay kit (Bio-Rad Laboratories, CA). Immunoblotting was conducted with standard protocols as described previously [55]. …”

Section: Methodsmentioning

confidence: 99%

The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition in gemcitabine resistance hepatoma cells

Wang

Hou

et al. 2015

Oncotarget

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Emerging evidence demonstrates that platelet-derived growth factor-D (PDGF-D) plays a critical role in epithelial-mesenchymal transition (EMT) and drug resistance in hepatocellular carcinoma (HCC) cells. However, the underlying mechanism has not been fully elucidated. The objective is to explore the molecular mechanism of PDGF-D-mediated EMT in drug resistance HCC cells. To achieve our goal, we used multiple approaches including Western blotting, real-time RT-PCR, wound healing assay, invasion assay, luciferase activity assay, transfection, and immunohistochemistry. We found that PDGF-D is highly expressed in gemcitabine-resistant (GR) HCC cells. Moreover, PDGF-D markedly inhibited miR-106a expression and subsequently upregulated Twist1 expression. Notably, PDGF-D expression was associated with miR-106a and Twist1 in HCC patients. Our findings provide a possible molecular mechanism for understanding GR chemoresistance in HCC cells. Therefore, inactivation of PDGF-D/Twist or activation of miR-106a could be a novel strategy for the treatment of HCC.

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Acquisition of epithelial–mesenchymal transition is associated with Skp2 expression in paclitaxel-resistant breast cancer cells

Cited by 92 publications

References 43 publications

Mechanisms of Resistance to Cabazitaxel

Mechanisms of Resistance to Cabazitaxel

MicroRNA-451 induces epithelial–mesenchymal transition in docetaxel-resistant lung adenocarcinoma cells by targeting proto-oncogene c-Myc

The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition in gemcitabine resistance hepatoma cells

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