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

Michihiko Kuwano, Tomohiro Shibata, Kosuke Watari, Mayumi Ono

研究成果: Contribution to journalReview article査読

37 被引用数 (Scopus)

抄録

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 YBX1 can predict poor outcomes in patients with more than 20 different tumor types. YBX1 is phosphorylated by kinases, including AKT, p70S6K, and p90RSK, and translocated into the nucleus to promote the transcription of resistance- and malignancy-related genes. Phosphorylated YBX1, therefore, plays a crucial role as a potent transcription factor in cancer. Herein, a novel anticancer therapeutic strategy is presented by targeting activated YBX1 to overcome drug resistance and malignant progression.

本文言語英語
ページ(範囲)1536-1543
ページ数8
ジャーナルCancer Science
110
5
DOI
出版ステータス出版済み - 5 2019

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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