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

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Abstract

Y‑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. KRAS gene 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 the KRAS mutation status and YB‑1 activity. In this review paper, we highlight the importance of the KRAS/YB‑1 cascade in the response of KRAS-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.

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Funding

This study was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG, TO 685/2-3).

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  1. Division of Radiobiology and Molecular Environmental Research, Department of Radiation Oncology, University of Tuebingen, Tuebingen, Germany

    Shayan Khozooei, Soundaram Veerappan &  Mahmoud Toulany

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  1. Shayan Khozooei
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  2. Soundaram Veerappan
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  3. Mahmoud Toulany
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Correspondence to Mahmoud Toulany.

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S. Khozooei, S. Veerappan and M. Toulany declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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S. Khozooei and S. Veerappan share first authorship.

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Khozooei, S., Veerappan, S. & Toulany, M. YB-1 activating cascades as potential targets in KRAS-mutated tumors. Strahlenther Onkol 199, 1110–1127 (2023). https://doi.org/10.1007/s00066-023-02092-8

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  • DOI: https://doi.org/10.1007/s00066-023-02092-8

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