The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells

Ge, Chun; Cao, Bei; Dong, Feng; Zhou, Fang; Zhang, Jingwei; Yang, Na; Feng, Suhua; Wang, Guangji; Aa, Jiye

doi:10.1038/s41598-017-03881-9

Cited by 51 publications

(40 citation statements)

References 43 publications

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“…SLC7A11 is associated with treatment resistance in breast cancer. Adriamycin suppresses SLC7A11 activity and causes overexpression of reactive oxygen species (ROS)-induced P-glycoprotein, resulting in drug resistance [ 63 ]. SLC7A11 is also responsible for distant metastasis of breast cancer.…”

Section: Amino Acid Transporters In Breast Cancermentioning

confidence: 99%

Amino Acid Transporters and Glutamine Metabolism in Breast Cancer

Jin

Kim

Koo

2018

IJMS

111

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Amino acid transporters are membrane transport proteins, most of which are members of the solute carrier families. Amino acids are essential for the survival of all types of cells, including tumor cells, which have an increased demand for nutrients to facilitate proliferation and cancer progression. Breast cancer is the most common malignancy in women worldwide and is still associated with high mortality rates, despite improved treatment strategies. Recent studies have demonstrated that the amino acid metabolic pathway is altered in breast cancer and that amino acid transporters affect tumor growth and progression. In breast cancer, glutamine is one of the key nutrients, and glutamine metabolism is closely related to the amino acid transporters. In this review, we focus on amino acid transporters and their roles in breast cancer. We also highlight the different subsets of upregulated amino acid transporters in breast cancer and discuss their potential applications as treatment targets, cancer imaging tracers, and drug delivery components. Glutamine metabolism as well as its regulation and therapeutic implication in breast cancer are also discussed.

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Section: Amino Acid Transporters In Breast Cancermentioning

confidence: 99%

Amino Acid Transporters and Glutamine Metabolism in Breast Cancer

Jin

Kim

Koo

2018

IJMS

111

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“…A previous study revealed that high levels of MDR1 and P-gp were associated with chemotherapy sensitivity, high-grade tumors, lymph node metastasis, a poor response and a shorter survival ( 25 ). Ge et al stated that ADM induced the overexpression of P-gp in breast cancer cells, which, in turn, increased the intracellular efflux of ADM ( 26 ). The present study further highlighted that K562/ADM cells were more resistant to ADM, which may provide new insight into leukemic therapies.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑145 promotes the apoptosis of leukemic�stem�cells and enhances drug‑resistant K562/ADM cell�sensitivity to adriamycin via the regulation of ABCE1

Wuxiao

Wang

et al. 2020

Int J Mol Med

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Leukemia is a type of cancer which originates in blood-forming tissues. MicroRNAs (miRNAs or miRs) have been shown to be involved leukemogenesis. In the present study, following the gain- and loss-function of miR-145 and ATP-binding cassette sub-family E member 1 (ABCE1) in K562 cells and K562 adriamycin-resistant cells (K562/ADM cells), the levels of multidrug resistance protein 1 (MRP1) and P-glycoprotein (P-gp) were measured. The viability of the K562 cells and K562/ADM cells treated with various concentrations of ADM, and cell sensitivity to ADM were measured. The apoptosis of stem cells was detected. K562/ADM cells were transfected with miR-145 mimic or with miR-145 mimic together with ABCE1 overexpression plasmid to examine the effects of ABCE1 on the sensitivity of K562/ADM cells to ADM. The association between miR-145 and ABCE1/MRP1 was then verified. The dose- and time-dependent effects of ADM on the K562 cells and K562/ADM cells were examined. The K562/ADM cells exhibited a greater resistance to ADM, higher levels of MRP1 and P-gp, and a lower miR-145 expression. The K562/ADM cells and stem cells in which miR-145 was overexpressed exhibited a suppressed cell proliferation, decreased MRP1 and P-gp levels, and an increased apoptotic rate. However, K562 cells with a low expression of miR-145 exhibited an increased cell proliferation, increased levels of MRP1 and P-gp, and a suppressed apoptotic rate. Compared with the overexpression of miR-145, the combination of miR-145 and ABCE1 decreased the sensitivity of drug-resistant K562/ADM cells to ADM. The above-mentioned effects of miR-145 were achieved by targeting ABCE1. Taken together, the findings of the present study demonstrate that the overexpression of miR-145 promotes leukemic stem cell apoptosis and enhances the sensitivity of K562/ADM cells to ADM by inhibiting ABCE1.

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“…Although downregulation of SLC7A11 inhibits GSH synthesis and induces oxidative stress, it leads to the increased expression of the efflux transporter P-glycoprotein (P-gp), also called multidrug resistance protein 1, MDR1, and therefore induces a drug-resistant phenotype in breast cancer cells. The study by Ge et al suggests that reversing the P-gp overexpression and potential collateral sensitivity of P-gp expressing cells to certain chemical drugs might be utilized to increase the anti-cancer potential of the SLC7A11-targeting agents [ 100 , 101 ].…”

Section: Amino Acid Transporters Upregulated In Tumors and Their Rmentioning

confidence: 99%

Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Kahya

Köseer

Dubrovska

2021

Cancers

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Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

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The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells

Cited by 51 publications

References 43 publications

Amino Acid Transporters and Glutamine Metabolism in Breast Cancer

Amino Acid Transporters and Glutamine Metabolism in Breast Cancer

MicroRNA‑145 promotes the apoptosis of leukemic�stem�cells and enhances drug‑resistant K562/ADM cell�sensitivity to adriamycin via the regulation of ABCE1

Amino Acid Transporters on the Guard of Cell Genome and Epigenome

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