YB-1 activating cascades as potential targets in KRAS-mutated tumors

AbstractY ‑box binding protein‑1 (YB-1) is a multifunctional protein that is highly expressed in human solid tumors of various entities. Several cellular processes,e.g. cell cycle progression, cancer stemness and DNA damage signaling that are involved in the response to chemoradiotherapy (CRT) are tightly governed by YB ‑1.KRASgene with about 30% mutations in all cancers, is considered the most commonly mutated oncogene in human cancers. Accumulating evidence indicates that oncogenic KRAS mediates CRT resistance. AKT and p90 ribosomal S6 kinase are downstream of KRAS and are the major kinases that stimulate YB ‑1 phosphorylation. Thus, there is a close link between theKRAS mutation status and YB ‑1 activity. In this review paper, we highlight the importance of the KRAS/YB‑1 cascade in the response ofKRAS-mutated solid tumors to CRT. Likewise, the opportunities to interfere with this pathway to improve CRT outcome are discussed in light of the current literature.
Source: Strahlentherapie und Onkologie - Category: Cancer & Oncology Source Type: research