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

Alkrekshi, Akram; Wang, Wei; Rana, Priyanka S.; Markovic, Vesna; Sossey‐Alaoui, Khalid

doi:10.1016/j.cellsig.2021.110073

Cited by 45 publications

(34 citation statements)

References 174 publications

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“…YB1 was shown to be associated with chemotherapy resistance in several types of cancer, including BC (reviewed in [ 16 ]). We interrogated the Cancer Cell Line Encyclopedia (CCLE) for the IC50 of three of the most commonly used chemotherapeutic agents for the treatment of patients with TNBC (Cisplatin, Docetaxel and Doxorubicin) in cell lines of the TNBC subtype; these included three AA and three CA TNBC cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, we posit that the residual levels of YB1 and its associated CSC markers is responsible for the enhanced aggressivity of the AA TNBC cell lines both in vitro ( Figure 3 ) and in vivo ( Figure 4 ). YB1 is also widely documented as a major player in the regulation of chemoresistance in several types of cancer, including BC (reviewed in [ 16 ]), which reenforces the association between YB1 and chemoresistance in AA TNBC tumors, given that AA TNBC are more prone to develop resistance to standards of care chemotherapies than their CA counterparts (reviewed in [ 16 ]). Our data show a clear and significant positive correlation between YB1 expression and the IC50 values of the chemotherapeutic drugs that are commonly used to treat TNBC tumors, in TNBC cell lines of AA origin ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

“…The Y Box binding protein 1 (YB1) is a multifunctional protein, found both in the cytoplasm and inside the nucleus, that belongs to the highly conserved Cold Shock Domain protein family [ 16 ]. Among its multitude of functions, YB1 is more known to be involved in the regulation of transcription, mRNA stability, and splicing [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer

Rana

Alkrekshi

Markovic

et al. 2021

Cancers

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Triple negative breast cancer (TNBC) is the most aggressive amongst all breast cancer (BC) subtypes. While TNBC tumors represent less than 20% of all BC subtypes, they are responsible for the most BC-related deaths. More significantly, when considering TNBC incidence across all racial/ethnic groups, TNBC accounts for less than 20% of all BCs. However, in non-Hispanic black women, the incidence rate of TNBC is more than 40%, which may be a contributing factor to the higher BC-related death rate in this population. These disparities remain strong even after accounting for differences in socioeconomic status, healthcare access, and lifestyle factors. Increased evidence now points to biological mechanisms that are intrinsic to the tumor that contribute to disparate TNBC disease burdens. Here, we show that YB1, a multifunction gene, plays a major role in the TNBC disparities between African American (AA) and Caucasian American (CA) women. We show in three independent TNBC tumors cohorts, that YB1 is significantly highly expressed in AA TNBC tumors when compared to CAs, and that increased levels of YB1 correlate with poor survival of AA patients with TNBC. We used a combination of genetic manipulation of YB1 and chemotherapy treatment, both in vitro and in animal models of TNBC to show that YB1 oncogenic activity is more enhanced in TNBC cell lines of AA origin, by increasing their tumorigenic and aggressive behaviors, trough the activation of cancer stem cell phenotype and resistance to chemotherapeutic treatments.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer

Rana

Alkrekshi

Markovic

et al. 2021

Cancers

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“…Then, 13 prognostic hub genes were identified from 626 mRNAsi-related genes using the LASSO regression models (Figure 3A,B). Among these hub genes, only RAMP3 showed a negative correlation with mRNAsi, while the other genes showed a positive correlation with mRNAsi including stem/progenitor cells regulators such as KPNA2 and YBX1 (Figure 3C,D) [46][47][48][49][50]. Then, multivariate Cox regression analysis was conducted to develop the HSRM based on the expression levels of 13 prognostic hub genes (Figure 3E).…”

Section: Training and Validation Of Hsrm Of Hcc Stemness In Five Hcc ...mentioning

confidence: 99%

Implications of Stemness Features in 1059 Hepatocellular Carcinoma Patients from Five Cohorts: Prognosis, Treatment Response, and Identification of Potential Compounds

Mai

Xie

Luo

et al. 2022

Cancers

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Cancer stemness has been reported to drive hepatocellular carcinoma (HCC) tumorigenesis and treatment resistance. In this study, five HCC cohorts with 1059 patients were collected to calculate transcriptional stemness indexes (mRNAsi) by the one-class logistic regression machine learning algorithm. In the TCGA-LIHC cohort, we found mRNAsi was an independent prognostic factor, and 626 mRNAsi-related genes were identified by Spearman correlation analysis. The HCC stemness risk model (HSRM) was trained in the TCGA-LIHC cohort and significantly discriminated overall survival in four independent cohorts. HSRM was also significantly associated with transarterial chemoembolization treatment response and rapid tumor growth in HCC patients. Consensus clustering was conducted based on mRNAsi-related genes to divide 1059 patients into two stemness subtypes. On gene set variation analysis, samples of subtype I were found enriched with pathways such as DNA replication and cell cycle, while several liver-specific metabolic pathways were inhibited in these samples. Somatic mutation analysis revealed more frequent mutations of TP53 and RB1 in the subtype I samples. In silico analysis suggested topoisomerase, cyclin-dependent kinase, and histone deacetylase as potential targets to inhibit HCC stemness. In vitro assay showed two predicted compounds, Aminopurvalanol-a and NCH-51, effectively suppressed oncosphere formation and impaired viability of HCC cell lines, which may shed new light on HCC treatment.

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“…Several review articles have recently summarized the function of YB-1 in various cancers [ 16 , 17 ]. In this review, we focus on newly described functions of YB-1 in cancer, encompassing its functions in the immune system and autophagy, its upstream regulation, post-translational modifications, and potential targeted strategies.…”

Section: Introductionmentioning

confidence: 99%

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

Yin

Zheng

Luo

et al. 2022

Cells

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Y box binding protein 1 (YB-1) is a protein with a highly conserved cold shock domain (CSD) that also belongs to the family of DNA- and RNA-binding proteins. YB-1 is present in both the nucleus and cytoplasm and plays versatile roles in gene transcription, RNA splicing, DNA damage repair, cell cycle progression, and immunity. Cumulative evidence suggests that YB-1 promotes the progression of multiple tumor types and serves as a potential tumor biomarker and therapeutic target. This review comprehensively summarizes the emerging functions, mechanisms, and regulation of YB-1 in cancers, and further discusses targeted strategies.

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

Cited by 45 publications

References 174 publications

YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer

YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer

Implications of Stemness Features in 1059 Hepatocellular Carcinoma Patients from Five Cohorts: Prognosis, Treatment Response, and Identification of Potential Compounds

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

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