Multidrug efflux transporter ABCG2: expression and regulation.

Autor: Kukal S; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Guin D; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India.; Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi, 110042, India., Rawat C; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Bora S; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India.; Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi, 110042, India., Mishra MK; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India.; Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi, 110042, India., Sharma P; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India., Paul PR; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Kanojia N; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Grewal GK; Department of Biotechnology, Kanya Maha Vidyalaya, Jalandhar, Punjab, 144004, India., Kukreti S; Nucleic Acids Research Lab, Department of Chemistry, University of Delhi (North Campus), Delhi, 110007, India., Saso L; Department of Physiology and Pharmacology 'Vittorio Erspamer', Sapienza University of Rome, P. le Aldo Moro 5, 00185, Rome, Italy., Kukreti R; Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India. ritus@igib.res.in.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. ritus@igib.res.in.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2021 Nov; Vol. 78 (21-22), pp. 6887-6939. Date of Electronic Publication: 2021 Sep 29.
DOI: 10.1007/s00018-021-03901-y
Abstrakt: The adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) was originally discovered in a multidrug-resistant breast cancer cell line. Studies in the past have expanded the understanding of its role in physiology, disease pathology and drug resistance. With a widely distributed expression across different cell types, ABCG2 plays a central role in ATP-dependent efflux of a vast range of endogenous and exogenous molecules, thereby maintaining cellular homeostasis and providing tissue protection against xenobiotic insults. However, ABCG2 expression is subjected to alterations under various pathophysiological conditions such as inflammation, infection, tissue injury, disease pathology and in response to xenobiotics and endobiotics. These changes may interfere with the bioavailability of therapeutic substrate drugs conferring drug resistance and in certain cases worsen the pathophysiological state aggravating its severity. Considering the crucial role of ABCG2 in normal physiology, therapeutic interventions directly targeting the transporter function may produce serious side effects. Therefore, modulation of transporter regulation instead of inhibiting the transporter itself will allow subtle changes in ABCG2 activity. This requires a thorough comprehension of diverse factors and complex signaling pathways (Kinases, Wnt/β-catenin, Sonic hedgehog) operating at multiple regulatory levels dictating ABCG2 expression and activity. This review features a background on the physiological role of transporter, factors that modulate ABCG2 levels and highlights various signaling pathways, molecular mechanisms and genetic polymorphisms in ABCG2 regulation. This understanding will aid in identifying potential molecular targets for therapeutic interventions to overcome ABCG2-mediated multidrug resistance (MDR) and to manage ABCG2-related pathophysiology.
(© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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