Dataset Information

TRPS1 Confers Multidrug Resistance of Breast Cancer Cells by Regulating BCRP Expression.

ABSTRACT: Multidrug resistance (MDR) is the major obstruction in the successful treatment of breast cancer (BCa). The elucidation of molecular events that confer chemoresistance of BCa is of major therapeutic importance. Several studies have elucidated the correlation of TRPS1 and BCa. Here we focused on the role of TRPS1 in acquisition of chemoresistance, and reported a unique role of TRPS1 renders BCa cells resistant to chemotherapeutic drugs via the regulation of BCRP expression. Bioinformation analysis based on publicly available BCa data suggested that TRPS1 overexpression linked to chemoresistance. Mechanistically, TRPS1 regulated BCRP expression and efflux transportation. Overexpression of TRPS1 led to upregulation of BCRP while its inhibition resulted in repression of BCRP. The correlation of TRPS1 and BCRP was further confirmed by immunohistochemistry in 180 BCa samples. MTT assay demonstrated that manipulation of TRPS1 expression affects the chemosensitivity of BCa cells. In total, high expression of TRPS1 confers MDR of BCa which is mediated by BCRP. Our data demonstrated a new insight into mechanisms and strategies to overcome chemoresistance in BCa.

SUBMITTER: Hu J

PROVIDER: S-EPMC7338551 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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TRPS1 Confers Multidrug Resistance of Breast Cancer Cells by Regulating BCRP Expression.

Hu Jing J Zhang Hui H Liu Long L Han Bo B Zhou Gengyin G Su Peng P

Frontiers in oncology 20200630

Multidrug resistance (MDR) is the major obstruction in the successful treatment of breast cancer (BCa). The elucidation of molecular events that confer chemoresistance of BCa is of major therapeutic importance. Several studies have elucidated the correlation of TRPS1 and BCa. Here we focused on the role of TRPS1 in acquisition of chemoresistance, and reported a unique role of TRPS1 renders BCa cells resistant to chemotherapeutic drugs via the regulation of BCRP expression. Bioinformation analysi ...[more]

PMID: 32695669

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Project description:Breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2) is an ATP-binding cassette (ABC) transporter identified as a molecular cause of multidrug resistance (MDR) in diverse cancer cells. BCRP physiologically functions as a part of a self-defense mechanism for the organism; it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract, as well as through the blood-brain, placental, and possibly blood-testis barriers. BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use. Thus, BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs. Because BCRP is also known to be a stem cell marker, its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance, self-renewal (stemness), and invasiveness (aggressiveness), and thereby impart a poor prognosis. Therefore, blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers. Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR. Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1α, estrogen receptor, and peroxisome proliferator-activated receptor. Furthermore, alternative promoter usage, demethylation of the BCRP promoter, and histone modification are likely associated with drug-induced BCRP overexpression in cancer cells. Finally, PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions. These biological events seem involved in a complicated manner. Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer. This review will present a synopsis of the impact of BCRP-mediated MDR in cancer cells, and the molecular mechanisms of acquired MDR currently postulated in a variety of human cancers.

Dataset Information

TRPS1 Confers Multidrug Resistance of Breast Cancer Cells by Regulating BCRP Expression.

Publications

TRPS1 Confers Multidrug Resistance of Breast Cancer Cells by Regulating BCRP Expression.

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