Open AccessOncogenic Y‐box binding protein‐1 as an effective therapeutic target in drug‐resistant cancer
Author(s) -
Kuwano Michihiko,
Shibata Tomohiro,
Watari Kosuke,
Ono Mayumi
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14006
Subject(s) - transcription factor , biology , cancer research , cancer cell , gene , cancer , drug resistance , genetics
Y‐box binding protein‐1 ( YBX 1), 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, ABCB 1 , as well as growth factor receptor genes, EGFR and HER 2/ErbB2 , was initially discovered to be transcriptionally activated by YBX 1 in cancer cells. Expression of other drug resistance‐related genes, MVP / LRP , TOP 2A , CD 44 , CD 49f , BCL 2 , MYC , and androgen receptor ( AR ), is also transcriptionally activated by YBX 1, consistently indicating that YBX 1 is involved in tumor drug resistance. Furthermore, there is strong evidence to support that nuclear localization and/or overexpression of YBX 1 can predict poor outcomes in patients with more than 20 different tumor types. YBX 1 is phosphorylated by kinases, including AKT , p70S6K, and p90 RSK , and translocated into the nucleus to promote the transcription of resistance‐ and malignancy‐related genes. Phosphorylated YBX 1, therefore, plays a crucial role as a potent transcription factor in cancer. Herein, a novel anticancer therapeutic strategy is presented by targeting activated YBX 1 to overcome drug resistance and malignant progression.