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Review
. 2021 Sep:85:110073.
doi: 10.1016/j.cellsig.2021.110073. Epub 2021 Jul 3.

A comprehensive review of the functions of YB-1 in cancer stemness, metastasis and drug resistance

Akram Alkrekshi  1 , Wei Wang  1 , Priyanka Shailendra Rana  1 , Vesna Markovic  2 , Khalid Sossey-Alaoui  3
Affiliations
Review

A comprehensive review of the functions of YB-1 in cancer stemness, metastasis and drug resistance

Akram Alkrekshi et al. Cell Signal. 2021 Sep.

Abstract

The Y Box binding protein 1 (YB-1) is a member of the highly conserved Cold Shock Domain protein family with multifunctional properties both in the cytoplasm and inside the nucleus. YB-1 is also involved in various cellular functions, including regulation of transcription, mRNA stability, and splicing. Recent studies have associated YB-1 with the regulation of the malignant phenotypes in several tumor types. In this review article, we provide an in-depth and expansive review of the literature pertaining to the multiple physiological functions of YB-1. We will also review the role of YB-1 in cancer development, progression, metastasis, and drug resistance in various malignancies, with more weight on literature published in the last decade. The methodology included querying databases PubMed, Embase, and Google Scholar for Y box binding protein 1, YB-1, YBX1, and Y-box-1.

Keywords: Cancer; Cancer stem cells;immunotherapy; Chemoresistance; Triple negative breast cancer; YB-1.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Structure of YB-1 depicting three domains; Ala/Pro-rich N-terminal domain (1–50), cold shock domain (51–128) with phosphorylation site at serine 102, and C-terminal domain (129–324). The sites of cytoplasmic retention site (CRS), nuclear localization signal (NLS) and S20 proteasome cleavage are shown.
Figure 2.
Figure 2.. Evolutionary conservation of the YBX gene family.
(A) Alignment (Clustal Omega; https://www.ebi.ac.uk/Tools/msa/clustalo/) of the human and mouse YBX amino acid sequences. YBX1, NP_004550; Ybx1, NP_035862; YBX2, NP_057066; Ybx2, NP_001334563; YBX3, NP_001138898; Ybx3, NP_620817. (B) Deduced phylogenetic tree of the YBX proteins using the Clustal Omega program. Based on the protein sequence alignments, the YBX gene family seem to have originated from a single ancestor closely related to YBX2, which had split during evolution to generate both YBx1 and YBX3.(C) Percent Identity Matrix between the human and mouse YBX proteins. The human and mouse YBX1 are almost 100% identical compared to their YBX2 and YBX3 orthologs, 88% and 87%, respectively.
Figure 2.
Figure 2.. Evolutionary conservation of the YBX gene family.
(A) Alignment (Clustal Omega; https://www.ebi.ac.uk/Tools/msa/clustalo/) of the human and mouse YBX amino acid sequences. YBX1, NP_004550; Ybx1, NP_035862; YBX2, NP_057066; Ybx2, NP_001334563; YBX3, NP_001138898; Ybx3, NP_620817. (B) Deduced phylogenetic tree of the YBX proteins using the Clustal Omega program. Based on the protein sequence alignments, the YBX gene family seem to have originated from a single ancestor closely related to YBX2, which had split during evolution to generate both YBx1 and YBX3.(C) Percent Identity Matrix between the human and mouse YBX proteins. The human and mouse YBX1 are almost 100% identical compared to their YBX2 and YBX3 orthologs, 88% and 87%, respectively.
Figure 3.
Figure 3.
Akt/PI3K, Ras/Raf/MAPK/ERK, mTOR, TGFβ/Smad2 all regulate YB-1. RSK phosphorylates YB-1 at S102 initiates translocation to the nucleus where YB-1 alters many genes related to oncogenesis. In the cytoplasm, YB-1 regulates mRNA translation and spliceosome
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