The Communication between the PI3K/AKT/mTOR Pathway and Y-Box Binding Protein-1 in Gynecological Cancer

Sobočan, Monika; Bračič, Suzana; Knez, Jure; Takač, Iztok; Haybaeck, Johannes

doi:10.3390/cancers12010205

Cited by 27 publications

(22 citation statements)

References 94 publications

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“…Beside PI3K and AKT inhibitors, drugs targeting the PI3K-Akt pathway include mTOR inhibitors, as mTOR kinase (Mechanistic Target Of Rapamycin Kinase) is part of the PI3K/Akt pathway. Trials investigating the role of different mTOR inhibitors in gynecological oncology are ongoing [45]. In vitro studies on vulvar cancer cell lines support the notion of application of mTOR inhibitors in VSCC treatment [10,46] These studies investigated Vistusertib (AZD2014) [10] belonging to the second generation of mTOR inhibitors, i.e.…”

Section: Discussionmentioning

confidence: 99%

Genes, pathways and vulvar carcinoma - New insights from next-generation sequencing studies

Zięba

Chechlińska

Kowalik

et al. 2020

Gynecologic Oncology

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Section: Discussionmentioning

confidence: 99%

Genes, pathways and vulvar carcinoma - New insights from next-generation sequencing studies

Zięba

Chechlińska

Kowalik

et al. 2020

Gynecologic Oncology

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“…For instance, patients with KMT2D mutations might benefit from aurora kinase inhibitors, as suggested by Williams et al [33], and recently shown in head, neck, and cervical cancer [42]. Nevertheless, the prognostic or therapeutic roles of the abnormalities in this pathway in VSCC are yet to be elucidated [43].…”

Section: Discussionmentioning

confidence: 97%

Molecular Landscape of Vulvar Squamous Cell Carcinoma

Carreras-Dieguez

Guerrero

Rodrigo-Calvo

et al. 2021

IJMS

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Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with dual pathogenesis, Human papillomavirus (HPV)-associated and HPV-independent, with a poorly explored molecular landscape. We aimed to summarize the findings of the series analyzing molecular hallmarks of this neoplasm. In January 2021, we conducted a comprehensive literature search using Pubmed Medline and Scopus to identify publications focused on genomic profiling of VSCC. Observational studies, including both prospective and retrospective designs, evaluating molecular alterations in VSCC were deemed eligible. A total of 14 studies analyzing 749 VSCC were identified. The study series were heterogeneous in HPV testing and sequencing strategies, included small sets of tumors and cancer genes, and commonly lacked survival analysis. Only one extensive targeted next-generation sequencing-based study comprised a large cohort of 280 VSCC. The mutated genes, their number, and frequencies were highly variable between the series. Overall, TP53 and CDKN2A, followed by PIK3CA, HRAS, and PTEN, were the most frequently studied and mutated genes. Mutations involved in the PI3K/AKT/mTOR pathway, including TP53, HRAS, KRAS, and PIK3CA, have been consistently reported across the studies. However, the role of individual mutations or pathways in the development of VSCC remains unclear. In conclusion, heterogeneity and the small sample size of available molecular series contribute to a limited view of the molecular landscape of VSCC. Large-scale genome- or exome-wide studies with robust HPV testing are necessary to improve the molecular characterization of VSCC.

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“…YBX3 and YBX1could convey profound anti- and pro-oncogenic effects on AKT pathway dependent cell transformation ( 38 ). In gynecological cancer, YBX1 was shown to be an important player impacting AKT and the downstream genes such as EGFR, Snail, or E-cadherin ( 39 ). Thus, these findings suggested that YBX3 and YBX superfamily were closely associated with PI3K/AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

YBX3 Mediates the Metastasis of Nasopharyngeal Carcinoma via PI3K/AKT Signaling

et al. 2021

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The metastasis of nasopharyngeal carcinoma (NPC) is a complex process associated with oncogenic dysfunction, the deciphering of which remains a challenge and requires more in-depth studies. Y-box protein 3 (YBX3) is a DNA/RNA binding protein associated with gene transcription, DNA repair, and the progression of various diseases. However, whether and how YBX3 affects the metastasis of NPC remains unknown. Thus, in this study, we aimed to investigate the role of YBX3 in the metastasis of NPC and determine its underlying mechanism. Interestingly, it was found that the expression of YBX3, which was associated with NPC metastasis, was upregulated in the clinical NPC tissues and cell lines. Moreover, we found that knockdown of YBX3 expression by lentivirus shRNA significantly suppressed NPC cells migration in vitro and metastasis in vivo. Mechanistically, RNA sequencing results suggested that the genes regulated by YBX3 were significantly enriched in cell adhesion molecules, cAMP signaling pathway, calcium signaling pathway, focal adhesion, PI3K/AKT signaling pathway, Ras signaling pathway, Rap1 signaling pathway, NF-κB signaling pathway, and Chemokine signaling pathway. Of these, PI3K/AKT signaling pathway contained the most genes. Accordingly, YBX3 knockdown decreased the activation of PI3K/AKT signaling pathway, thereby inhibit epithelial-to-mesenchymal transition (EMT) and MMP1. These results have demonstrated that YBX3 are involved in the metastasis of NPC through regulating PI3K/AKT signaling pathway, and serve as a potential therapeutic target for patients with NPC.

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The Communication between the PI3K/AKT/mTOR Pathway and Y-Box Binding Protein-1 in Gynecological Cancer

Cited by 27 publications

References 94 publications

Genes, pathways and vulvar carcinoma - New insights from next-generation sequencing studies

Genes, pathways and vulvar carcinoma - New insights from next-generation sequencing studies

Molecular Landscape of Vulvar Squamous Cell Carcinoma

YBX3 Mediates the Metastasis of Nasopharyngeal Carcinoma via PI3K/AKT Signaling

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