Nuclear translocation of MRP1 contributes to multidrug resistance of mucoepidermoid carcinoma

Cai, Bingchu; Xu, Xiao; Fu, Shan-Min; Shen, Liangliang; Zhang, Jing; Guan, Su-Min; Wu, Jun-Zheng

doi:10.1016/j.oraloncology.2011.08.005

Cited by 16 publications

(18 citation statements)

References 24 publications

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“…12 As a result, chemotherapy is used for patient palliation, although ineffective for actual treatment. 30 Improved understanding of the pathobiology of the disease leading to rationally designed targeted therapies are necessary to improve the outcome of patients with mucoepidermoid carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Salivary gland cancer stem cells

2013

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Emerging evidence suggests the existence of a tumorigenic population of cancer cells that demonstrate stem cell-like properties such as self-renewal and multipotency. These cells, termed cancer stem cells (CSC), are able to both initiate and maintain tumor formation and progression. Studies have shown that CSC are resistant to traditional chemotherapy treatments preventing complete eradication of the tumor cell population. Following treatment, CSC are able to re-initiate tumor growth leading to patient relapse. Salivary gland cancers are relatively rare but constitute a highly significant public health issue due to the lack of effective treatments. In particular, patients with mucoepidermoid carcinoma or adenoid cystic carcinoma, the two most common salivary malignancies, have low long-term survival rates due to the lack of response to current therapies. Considering the role of CSC in resistance to therapy in other tumor types, it is possible that this unique sub-population of cells is involved in resistance of salivary gland tumors to treatment. Characterization of CSC can lead to better understanding of the pathobiology of salivary gland malignancies as well as to the development of more effective therapies. Here, we make a brief overview of the state-of-the-science in salivary gland cancer, and discuss possible implications of the cancer stem cell hypothesis to the treatment of salivary gland malignancies.

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Section: Introductionmentioning

confidence: 99%

Salivary gland cancer stem cells

2013

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“…Nuclear translocation of MRP-1 confers multidrug resistance to cancer cells (67). This work provides the first evidence suggesting that MRP-1 interacts with NLS-directed YB-1 to reach the nucleus.…”

Section: Discussionmentioning

confidence: 68%

Multidrug Resistance-associated Protein-1 (MRP-1)-dependent Glutathione Disulfide (GSSG) Efflux as a Critical Survival Factor for Oxidant-enriched Tumorigenic Endothelial Cells

Biswas

Khanna

Spieldenner

et al. 2016

Journal of Biological Chemistry

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“…In our previous study, we found nuclear MRP1 in MEC cells for the first time and proved that nuclear translocation of MRP1 was one of the reasons leading to multidrug-resistance of MC3/5FU cells [13]. To explore why the downregulation of MRP1 reversed the resistance to taxol which is not the substrate of MRP1 [13] but the substrate of MDR1 [9], we investigated MDR1 expression in MC3/5FU cells when MRP1 was downregulated through short-hairpin RNAs (shRNA) in this study.…”

Section: Introductionmentioning

confidence: 74%

“…To explore why the downregulation of MRP1 reversed the resistance to taxol which is not the substrate of MRP1 [13] but the substrate of MDR1 [9], we investigated MDR1 expression in MC3/5FU cells when MRP1 was downregulated through short-hairpin RNAs (shRNA) in this study. We also investigated the expression pattern of MDR1 and MRP1 in 127 cases of MEC patients by immunohistochemistry and explored the correlation between MRP1 and MDR1 in MEC.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Multidrug-Resistance Related Protein 1 Contributes to Multidrug-Resistance of Mucoepidermoid Carcinoma Mainly via Regulating Multidrug-Resistance Protein 1: A Human Mucoepidermoid Carcinoma Cells Model and Spearman's Rank Correlation Analysis

et al. 2013

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BackgroundMultidrug resistance-related protein 1 (MRP1/ABCC1) and multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1) are both membrane-bound drug transporters. In contrast to MDR1, MRP1 also transports glutathione (GSH) and drugs conjugated to GSH. Due to its extraordinary transport properties, MRP1/ABCC1 contributes to several physiological functions and pathophysiological incidents. We previously found that nuclear translocation of MRP1 contributes to multidrug-resistance (MDR) of mucoepidermoid carcinoma (MEC). The present study investigated how MRP1 contributes to MDR in the nuclei of MEC cells.MethodsWestern blot and RT-PCR was carried out to investigate the change of multidrug-resistance protein 1 (MDR1) in MC3/5FU cells after MRP1 was downregulated through RNA interference (RNAi). Immunohistochemistry (IHC) staining of 127 cases of MEC tissues was scored with the expression index (EI). The EI of MDR1 and MRP1 (or nuclear MRP1) was analyzed with Spearman's rank correlation analysis. Using multiple tumor tissue assays, the location of MRP1 in other tissues was checked by HIC. Luciferase reporter assays of MDR1 promoter was carried out to check the connection between MRP1 and MDR1 promoter.ResultsMRP1 downregulation led to a decreased MDR1 expression in MC3/5FU cells which was caused by decreased activity of MDR1 promoter. IHC study of 127 cases of MEC tissues demonstrated a strong positive correlation between nuclear MRP1 expression and MDR1 expression. Furthermore, IHC study of multiple tumor tissue array sections showed that although nuclear MRP1 widely existed in MEC tissues, it was not found in normal tissues or other tumor tissues.ConclusionsOur findings indicate that nuclear MRP1 contributes to MDR mainly through regulating MDR1 expression in MEC. And the unique location of MRP1 made it an available target in identifying MEC from other tumors.

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Nuclear translocation of MRP1 contributes to multidrug resistance of mucoepidermoid carcinoma

Cited by 16 publications

References 24 publications

Salivary gland cancer stem cells

Salivary gland cancer stem cells

Multidrug Resistance-associated Protein-1 (MRP-1)-dependent Glutathione Disulfide (GSSG) Efflux as a Critical Survival Factor for Oxidant-enriched Tumorigenic Endothelial Cells

Nuclear Multidrug-Resistance Related Protein 1 Contributes to Multidrug-Resistance of Mucoepidermoid Carcinoma Mainly via Regulating Multidrug-Resistance Protein 1: A Human Mucoepidermoid Carcinoma Cells Model and Spearman's Rank Correlation Analysis

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