The role of ABC transporters in ovarian cancer progression and chemoresistance

Ween, Miranda P.; Armstrong, Mark; Oehler, Martin K.; Ricciardelli, Carmela

doi:10.1016/j.critrevonc.2015.05.012

Cited by 148 publications

(162 citation statements)

References 423 publications

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“…Members in the ABC-C subfamily have been recognized as export pumps for amphiphilic anions especially for conjugates of lipophilic compounds with glutathione or several other non-toxic anionic residues in Saccharomyces cerevisiae [10,37,38,39]. Δ FgABCC9 showed slower mycelial growth on mSNA plates than WT and C- FgABCC9 (Figure 2a), which suggested that FgABCC9 is also an exporter for other materials that are essential for normal growth of F. graminearum .…”

Section: Discussionmentioning

confidence: 99%

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Fusarium graminearum ATP-Binding Cassette Transporter Gene FgABCC9 Is Required for Its Transportation of Salicylic Acid, Fungicide Resistance, Mycelial Growth and Pathogenicity towards Wheat

Zhang

Liu

et al. 2018

IJMS

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ATP-binding cassette (ABC) transporters hydrolyze ATP to transport a wide range of substrates. Fusarium graminearum is a major causal agent of Fusarium head blight, which is a severe disease in wheat worldwide. FgABCC9 (FG05_07325) encodes an ABC-C (ABC transporter family C) transporter in F. graminearum, which was highly expressed during the infection in wheat and was up-regulated by the plant defense hormone salicylic acid (SA) and the fungicide tebuconazole. The predicted tertiary structure of the FgABCC9 protein was consistent with the schematic of the ABC exporter. Deletion of FgABCC9 resulted in decreased mycelial growth, increased sensitivity to SA and tebuconazole, reduced accumulation of deoxynivalenol (DON), and less pathogenicity towards wheat. Re-introduction of a functional FgABCC9 gene into ΔFgABCC9 recovered the phenotypes of the wild type strain. Transgenic expression of FgABCC9 in Arabidopsis thaliana increased the accumulation of SA in its leaves without activating SA signaling, which suggests that FgABCC9 functions as an SA exporter. Taken together, FgABCC9 encodes an ABC exporter, which is critical for fungal exportation of SA, response to tebuconazole, mycelial growth, and pathogenicity towards wheat.

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Section: Discussionmentioning

confidence: 99%

“…Members of this superfamily have conserved domain architecture and have been divided into seven families (A–G) in fungi, plants, and animals [8,9,10]. Recent studies demonstrated that the ABC transporter family C (ABC-C) as a cell membrane protein is important for fungal pathogens in response to fungicide [11,12,13].…”

Section: Introductionmentioning

confidence: 99%

Fusarium graminearum ATP-Binding Cassette Transporter Gene FgABCC9 Is Required for Its Transportation of Salicylic Acid, Fungicide Resistance, Mycelial Growth and Pathogenicity towards Wheat

Zhang

Liu

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…Such proteins belong to a large family of 49 genes, classified in seven subfamilies (A-G), with several transporters involved in MDR [11]. These include P-glycoprotein (P-gp or ABCB1), multidrug resistance associated proteins 1-6 (MRP1-6 or ABCC1-6), and breast cancer resistance protein (BCRP or ABCG2) [12]. P-gp is the best characterized efflux pump mediating MDR due to its broadest substrate specificity and widest tissue and organ distribution.…”

Section: Introductionmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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“…17 Without patient preselection, the potential effects in patients with Pgp overexpression could be masked by the patients that do not express this transporter. 17, 18 Thus, the success of any Pgp targeted therapeutics depends on a companion diagnostic test that can detect tumoral Pgp expression in a patient and to determine if favorable outcome will come from the specific treatments.…”

Section: Introductionmentioning

confidence: 99%

Molecular Imaging of P-glycoprotein in Chemoresistant Tumors Using a Dual-Modality PET/Fluorescence Probe

et al. 2017

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Overexpression of P-glycoprotein (Pgp) has been considered a primary cause for multidrug resistance in a variety of cancers for three decades. However, clinical translation of Pgp targeted therapeutics has been hindered by lack of patient preselection based on the Pgp presence in tumors. We aim to develop a molecularly targeted probe for imaging tumoral Pgp in vivo with positron emission tomography (PET) and fluorescence, and to provide a tool for preselecting the patients with tumoral Pgp expression. Thus, a Pgp monoclonal antibody 15D3 was chemically modified with IRDye800 (IR800) and DOTA chelator. The specificity of the antibody conjugates DOTA-Pab-IR800 was evaluated in Pgp-expressing 3T3-MDR1 and control 3T3 cells. After radiolabeling with 64Cu, the probe was applied in small animal PET imaging of Pgp in a mouse xenograft model of NCI/ADR-Res cells, which are chemoresistant through overexpression of Pgp. Quantification analysis of the PET images demonstrated that the tumor uptake of the radioactive probe was 9.9 ± 1.4, 12.1 ± 1.2, and 10.5 ± 1.0%ID/g at 4, 24, and 48h post injection. The tumor-to-muscle ratio was 20.9 at 48 h post injection based on biodistribution studies. Fluorescence imaging was performed following PET experiments, and it demonstrated excellent tumor accumulation of this dual-modality probe in the NCI/ADR-Res tumors. Further, an image-guided surgery was performed successfully using the fluorescence modality of the probe, demonstrating potential utility of this probe in image-guided surgical removal of Pgp-positive drug resistant tumors in the patients. In conclusion, this study clearly demonstrated that the Pgp-targeted antibody probe, 64Cu-DOTA-Pab-IR800, could provide a promising diagnosis tool for detection of Pgp-expressing tumors in vivo.

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The role of ABC transporters in ovarian cancer progression and chemoresistance

Cited by 148 publications

References 423 publications

Fusarium graminearum ATP-Binding Cassette Transporter Gene FgABCC9 Is Required for Its Transportation of Salicylic Acid, Fungicide Resistance, Mycelial Growth and Pathogenicity towards Wheat

Fusarium graminearum ATP-Binding Cassette Transporter Gene FgABCC9 Is Required for Its Transportation of Salicylic Acid, Fungicide Resistance, Mycelial Growth and Pathogenicity towards Wheat

Marine Natural Products as Models to Circumvent Multidrug Resistance

Molecular Imaging of P-glycoprotein in Chemoresistant Tumors Using a Dual-Modality PET/Fluorescence Probe

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