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Interactions between the ABCG2 multidrug transporter and inhibitors of the EGFR signaling pathway
Author(s) -
Sarkadi Balazs,
Hegedüs Csilla,
Truta-Feles Krisztina,
Özvegy-Laczka Csilla,
Telbisz Agnes,
Várady György
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.799.6
Subject(s) - abcg2 , multiple drug resistance , side population , transporter , cancer stem cell , cancer cell , cancer , intracellular , efflux , pharmacology , chemistry , cytotoxic t cell , signal transduction , drug resistance , population , cancer research , biology , microbiology and biotechnology , atp binding cassette transporter , biochemistry , medicine , in vitro , genetics , gene , environmental health
Human ABCG2 is a plasma membrane glycoprotein that provides protection against xenobiotics and causes drug resistance in cancer. ABCG2 was also found to be a key protein in the side population (SP) of normal and cancer stem cells. Since up‐regulation of the EGFR‐dependent signaling plays an important role in several types of cancer, EGFR inhibition by small molecules is by now widely applied at the clinics. We have studied the potential role of ABCG2 expression on the effects of various EGFR inhibitors and found that the presence of ABCG2 significantly modified the intracellular effects of these signaling inhibitors. On the other hand, some of these agents also inhibited ABCG2 function, thereby re‐sensitizing multidrug resistant cancer cells to other cytotoxic agents. We describe a complex interplay between clinically relevant small molecule inhibitors of the EGFR signaling pathway and ABCG2, which can influence drug resistance of cancer cells and especially of cancer stem cells.