Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating MDR1 transcription

Chen, Shuai; Wang, Han; Li, Zhi; You, Jun; Wu, Qiu-Wan; Zhao, Can; Tzeng, Chi-Meng; Zhang, Zhiming

doi:10.1038/s41416-018-0119-5

Cited by 30 publications

(35 citation statements)

References 42 publications

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“…The work by Chen et al implicates WBP2 in the resistance of MCF-7 cells to doxorubicin. Overexpression of WBP2 promoted its interaction with ER, which in turn enhanced ER-mediated transcription of multidrug resistance gene (MDR1) [84].…”

Section: Translational and Clinical Significance Of Wbp2mentioning

confidence: 99%

The emerging roles of WBP2 oncogene in human cancers

et al. 2020

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WW domain-binding protein 2 (WBP2) is an emerging oncoprotein. Over the past decade, WBP2 surfaced as a key node connecting key signaling pathways associated with ER/PR, EGFR, PI 3 K, Hippo, and Wnt in cancer. In addition to the oncogenic functions of WBP2, this review discusses the latest research regarding the multilevel regulation and modes of action of WBP2 and how they can be exploited for molecular medicine. In translational research, evidence supports the role of WBP2 as a biomarker for early detection, prognosis, and companion diagnostics in breast cancer. Finally, we envision new trends in WBP2 research in the space of molecular etiology of cancer, targeted therapeutics, and precision medicine.

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Section: Translational and Clinical Significance Of Wbp2mentioning

confidence: 99%

The emerging roles of WBP2 oncogene in human cancers

et al. 2020

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“…Chemotherapy is a commonly used strategy for treatment of breast cancer. But severe systemic side effects and drug resistance are frequent problems during chemotherapy (Barry, Alvarez, Scully, Miller, & Lipshultz, ; S. Chen et al, ). Therefore, it is necessary to explore and develop novel and effective anti‐breast cancer agents.…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity and molecular mechanisms of α‐conidendrin, a polyphenolic compound present in Taxus yunnanensis, on human breast cancer cell lines

Hafezi

Hemmati

Abbaszadeh

et al. 2020

Phytotherapy Research

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α-Conidendrin is a polyphenolic compound found mainly in Taxus yunnanensis, as the source of chemotherapy drug paclitaxel, which has been used in traditional medicine for treatment of cancer. This study aimed to investigate the anticancer activity and molecular mechanisms of α-conidendrin on breast cancer cell lines. The results of the present study show that α-conidendrin possesses potent antiproliferative effects on breast cancer cell lines MCF-7 and MDA-MB-231. α-Conidendrin significantly induced apoptosis in breast cancer cells via reactive oxygen species generation, upregulation of p53 and Bax, downregulation of Bcl-2, depolarization of mitochondrial membrane potential (MMP), release of cytochrome c from mitochondria, and activation of caspases-3 and -9. α-Conidendrin remarkably inhibited the proliferation of breast cancer cells through induction of cell cycle arrest by upregulating p53 and p21 and downregulating cyclin D1 and CDK4. Unlike breast cancer cells, the antiproliferative effect of α-conidendrin on human foreskin fibroblast cells (normal cells) was very small. In normal cells, reactive oxygen species levels, loss of MMP, release of cytochrome c, mRNA expression of p53, p21, cyclin D1, CDK4, Bax, and Bcl-2 as well as mRNA expression and activity of caspases-3 and -9 were significantly less affected by α-conidendrin compared with cancer cells. These results suggest that α-conidendrin can be a promising agent for treatment of breast cancer with little or no toxicity against normal cells. K E Y W O R D S apoptosis, breast cancer, cell cycle, polyphenolic compound, α-conidendrin

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“…Chemoresistance in cancer cells was associated with the EMT and upregulation of ABC transporters could be an evolutionarily conserved system. The overexpression of MDR1 could be conducive to both initiation and acceleration of the chemotherapy resistance in breast cancer cells [41]. Saxena M. et al suggested that chemotherapeutic drug-induced EMT increased the expression of ABC transporters and induced both the drug resistance and the invasion in breast cancer cells [34].…”

Section: Discussionmentioning

confidence: 99%

Deficiency in Dipeptidyl Peptidase-4 Promotes Chemoresistance Through the CXCL12/CXCR4/mTOR/TGFβ Signaling Pathway in Breast Cancer Cells

Yang

Kumagai

et al. 2020

IJMS

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Dipeptidyl peptidase (DPP)-4, a molecular target of DPP-4 inhibitors, which are type 2 diabetes drugs, is expressed in a variety of cell types, tissues and organs. DPP-4 has been shown to be involved in cancer biology, and we have recently shown that a DPP-4 inhibitor promoted the epithelial mesenchymal transition (EMT) in breast cancer cells. The EMT is known to associate with chemotherapy resistance via the induction of ATP-binding cassette (ABC) transporters in cancer cells. Here, we demonstrated that deficiency in DPP-4 promoted chemotherapy resistance via the CXCL12/CXCR4/mTOR axis, activating the TGFβ signaling pathway via the expression of ABC transporters. DPP-4 inhibition enhanced ABC transporters in vivo and in vitro. Doxorubicin (DOX) further induced ABC transporters in DPP-4-deficient 4T1 cells, and the induction of ABC transporters was suppressed by either the CXCR4 inhibitor AMD3100, the mTOR inhibitor rapamycin or a neutralizing TGFβ (1, 2 and 3) antibody(N-TGFβ). Knockdown of snail, an EMT-inducible transcription factor, suppressed ABC transporter levels in DOX-treated DPP-4-deficient 4T1 cells. In an allograft mouse model, however, the effects of DOX in either primary tumor or metastasis were not statistically different between control and DPP-4-kd 4T1. Taken together, our findings suggest that DPP-4 inhibitors potentiate chemotherapy resistance via the induction of ABC transporters by the CXCL12/CXCR4/mTOR/TGFβ signaling pathway in breast cancer cells.

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Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating MDR1 transcription

Abstract: Our finding provides a new mechanism for the chemotherapy response of ERα-positive breast tumours, and WBP2 might be a key molecule for developing new therapeutic strategies to treat chemoresistance in breast cancer patients.

Cited by 30 publications

References 42 publications

The emerging roles of WBP2 oncogene in human cancers

The emerging roles of WBP2 oncogene in human cancers

Anticancer activity and molecular mechanisms of α‐conidendrin, a polyphenolic compound present in Taxus yunnanensis, on human breast cancer cell lines

Deficiency in Dipeptidyl Peptidase-4 Promotes Chemoresistance Through the CXCL12/CXCR4/mTOR/TGFβ Signaling Pathway in Breast Cancer Cells

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