Oncogenic Y‐box binding protein‐1 as an effective therapeutic target in drug‐resistant cancer

摘要

Y‐box binding protein‐1 (YBX1), a multifunctional oncoprotein containing an evolutionarily conserved cold shock domain, dysregulates a wide range of genes involved in cell proliferation and survival, drug resistance, and chromatin destabilization by cancer. Expression of a multidrug resistance‐associated ATP binding cassette transporter gene, ABCB1, as well as growth factor receptor genes, EGFR and HER2/ErbB2, was initially discovered to be transcriptionally activated by YBX1 in cancer cells. Expression of other drug resistance‐related genes, MVP/LRP,TOP2A,CD44,CD49f,BCL2,MYC, and androgen receptor (AR), is also transcriptionally activated by YBX1, consistently indicating that YBX1 is involved in tumor drug resistance. Furthermore, there is strong evidence to support that nuclear localization and/or overexpression of style="fixed-case">YBX1 can predict poor outcomes in patients with more than 20 different tumor types. style="fixed-case">YBX1 is phosphorylated by kinases, including style="fixed-case">AKT, p70S6K, and p90 style="fixed-case">RSK, and translocated into the nucleus to promote the transcription of resistance‐ and malignancy‐related genes. Phosphorylated style="fixed-case">YBX1, therefore, plays a crucial role as a potent transcription factor in cancer. Herein, a novel anticancer therapeutic strategy is presented by targeting activated style="fixed-case">YBX1 to overcome drug resistance and malignant progression.