Insights on the structure–function relationship of human multidrug resistance protein 7 (MRP7/ABCC10) from molecular dynamics simulations and docking studies

Wang, Jing-Quan; Cui, Qingbin; Lei, Zi‐Ning; Teng, Quincy; Ji, Ning; Lin, Lusheng; Liu, Zhijun; Chen, Zhe-Sheng

doi:10.1002/mco2.65

Cited by 8 publications

(10 citation statements)

References 82 publications

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“…The cryo‐EM structure of ABCC1 92 , ABCC8 93 were reported, while the information of other transporters are from X‐ray diffraction or remained unknown. Recently, a homology‐model‐based molecular dynamic study regarding ABCC10 was reported by our group 94 . Structurally, ABCC1‐3 and ABCC6/8/9/10 have an additional N‐terminal TMD (TMD 0 ) that is smaller than the core TMD 95 .…”

Section: Abc Transporter Subfamilies: Structure Function and The Rela...mentioning

confidence: 99%

ATP‐binding cassette (ABC) transporters in cancer: A review of recent updates

Wang

Yang

et al. 2021

J Evidence Based Medicine

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The ATP-binding cassette (ABC) transporter superfamily is one of the largest membrane protein families existing in wide spectrum of organisms from prokaryotes to human. ABC transporters are also known as efflux pumps because they mediate the cross-membrane transportation of various endo-and xenobiotic molecules energized by ATP hydrolysis. Therefore, ABC transporters have been considered closely to multidrug resistance (MDR) in cancer, where the efflux of structurally distinct chemotherapeutic drugs causes reduced itherapeutic efficacy. Besides, ABC transporters also play other critical biological roles in cancer such as signal transduction. During the past decades, extensive efforts have been made in understanding the structure-function relationship, transportation profile of ABC transporters, as well as the possibility to overcome MDR via targeting these transporters. In this review, we discuss the most recent knowledge regarding ABC transporters and cancer drug resistance in order to provide insights for the development of more effective therapies. INTRODUCTIONSince the first discovery of the membrane transport protein Pglycoprotein (P-gp) or ATP-binding cassette (ABC) transporter B1 (ABCB1) in resistant cancer cells in the mid-1970s, more and more members in ABC transporter superfamily such as ABCG2 (breast cancer resistance protein, BCRP) and MRPs (multidrug resistance proteins) were discovered and characterized, especially the structurefunction relationship and their roles in tumorigenesis 1 (Figure 1). ABC transporter proteins are best known for mediating multidrug resistance (MDR) in cancer and lead to failure of chemotherapy. Besides, studies also revealed their critical roles in cancer as more than efflux pumps. 2,3 ABC transporter superfamily is composed of 7 subfamilies, namely ABCA to ABCG In human the ABC transporter superfamily is divided into least 48 members with different functions.

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Section: Abc Transporter Subfamilies: Structure Function and The Rela...mentioning

confidence: 99%

ATP‐binding cassette (ABC) transporters in cancer: A review of recent updates

Wang

Yang

et al. 2021

J Evidence Based Medicine

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“…In our study, we also found that MRP7 altered the cell morphology and promoted cell migration via upregulating the EMT marker N-cadherin. Although functionally active ABC transporters have generally been observed in both the cell membrane and intracellular vesicles, MRP7 in particular has been demonstrated earlier to exert its main effect at the cell membrane (49). The immunofluorescence assay and membrane/ cytoplasm protein immunoblotting showed that the MRP7 protein mainly localized on cell membrane.…”

Section: Discussionmentioning

confidence: 93%

Establishment and Characterization of a Novel Multidrug Resistant Human Ovarian Cancer Cell Line With Heterogenous MRP7 Overexpression

Wang

Yang

et al. 2021

Front. Oncol.

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Ovarian cancer is one of the leading female malignancies which accounts for the highest mortality rate among gynecologic cancers. Surgical cytoreduction followed by chemotherapy is the mainstay of treatment. However, patients with recurrent ovarian cancer are likely to exhibit resistance to chemotherapy due to reduced sensitivity to chemotherapeutic drugs. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been extensively studied as multidrug resistance (MDR) mediators since they are responsible for the efflux of various anticancer drugs. Multidrug resistance protein 7 (MRP7, or ABCC10) was discovered in 2001 and revealed to transport chemotherapeutic drugs. Till now, only limited knowledge was obtained regarding its roles in ovarian cancer. In this study, we established an MRP7-overexpressing ovarian cancer cell line SKOV3/MRP7 via transfecting recombinant MRP7 plasmids. The SKOV3/MRP7 cell line was resistant to multiple anticancer drugs including paclitaxel, docetaxel, vincristine and vinorelbine with a maximum of 8-fold resistance. Biological function of MRP7 protein was further determined by efflux-accumulation assays. Additionally, MTT results showed that the drug resistance of the SKOV3/MRP7 cells was reversed by cepharanthine, a known inhibitor of MRP7. Moreover, we also found that the overexpression of MRP7 enhanced the migration and epithelial-mesenchymal transition (EMT) induction. In conclusion, we established an in vitro model of MDR in ovarian cancer and suggested MRP7 overexpression as the leading mechanism of chemoresistance in this cell line. Our results demonstrated the potential relationship between MRP7 and ovarian cancer MDR.

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“…(2) The overexpression of MRPs such as MRP1, MRP2, and MRP7 is associated with poor chemotherapeutic outcomes in several cancers including breast cancer and lung cancer. Among these MRPs, MRP1 has been widely studied in the development of therapeutic strategies for drug resistant cancer [73,74]. Resveratrol (RSV), which is a polyphenol comes from grape and Chinese medicine Rhizoma polygoni cuspidati, was found to downregulate the expression of MRP1 and P-gp in DOX-resistant breast cancer cells, promoting the accumulation of DOX in resistant cells and thus enhancing the effects of chemotherapy in MDA-MB-231/ADR tumor-bearing mice [75].…”

Section: Reversal Of Drug Resistancementioning

confidence: 99%

Active Ingredients from Chinese Medicine for Combination Cancer Therapy

Wang¹,

Li²,

Chen³

et al. 2023

Int. J. Biol. Sci.

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Combination therapy against cancer has gained increasing attention because it can help to target multiple pathways to tackle oncologic progression and improve the limited antitumor effect of single-agent therapy. Chinese medicine has been studied extensively in cancer therapy and proven to be efficacious in many cases due to its wide spectrum of anticancer activities. In this review, we aim to summarize the recent progress of active ingredients from Chinese medicine (AIFCM) in combination with various cancer therapeutic modalities, including chemotherapy, gene therapy, radiotherapy, phototherapy and immunotherapy. In addition to highlighting the potential contribution of AIFCM in combination cancer therapy, we also elucidate the underlying mechanisms behind their synergistic effect and improved anticancer efficacy, thereby encouraging the inclusion of these AIFCM as part of effective armamentarium in fighting intractable cancers. Finally, we present the challenges and future perspectives of AIFCM combination therapy as a feasible and promising strategy for the optimization of cancer treatment and better clinical outcomes.

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Insights on the structure–function relationship of human multidrug resistance protein 7 (MRP7/ABCC10) from molecular dynamics simulations and docking studies

Cited by 8 publications

References 82 publications

ATP‐binding cassette (ABC) transporters in cancer: A review of recent updates

ATP‐binding cassette (ABC) transporters in cancer: A review of recent updates

Establishment and Characterization of a Novel Multidrug Resistant Human Ovarian Cancer Cell Line With Heterogenous MRP7 Overexpression

Active Ingredients from Chinese Medicine for Combination Cancer Therapy

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