VHL Expression in Kidney Cancer: Relation to Metastasis Development, Transcription and Growth Factors and Component of Akt/m-TOR Signaling Pathway

Спирина, Л. В.; Кондакова, И. В.; Yurmazov, Z. A.; Усынин, Е. А.; Slonimskaya, Е. М.; Lushnikova, N A; Podnebesnova, D V

doi:10.1007/s10517-019-04596-9

Cited by 4 publications

(5 citation statements)

References 13 publications

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“…HIF1α is one of the downstream proteins of mTOR (33). Previous studies have demonstrated that activated mTOR can maintain the stability of HIF1α (34,35).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of KRT17 decreases osteosarcoma cell proliferation and the Warburg effect via the AKT/mTOR/HIF1α pathway

Yan

Yang

et al. 2020

Oncol Rep

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Keratins are fibrous structural proteins that serve essential roles in forming the stratum corneum and protect the cells in this layer of skin from damage. Keratin 17 (KRT17) is a key member of the keratins, and dysregulated expression of KRT17 has been reported in various types of cancer, such as lung and gastric cancer. The present study aimed to identify the role of KRT17 in osteosarcoma and the underlying molecular mechanism. The expression of KRT17 in osteosarcoma tissues and cell lines was detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting. The effects of KRT17 on osteosarcoma cell proliferation and the Warburg effect in vitro were detected using CCK-8 and colony formation assays, cell cycle distribution analysis and metabolic measures. The effects of KRT17 on osteosarcoma cell proliferation in vivo were detected using a subcutaneous tumorigenesis model. The association between KRT17 and the AKT/mTOR/hypoxia-inducible factor 1α (HIF1α) pathway was detected using RT-qPCR and western blotting. The results demonstrated that KRT17 was highly expressed in osteosarcoma tissues and cell lines. Knockdown of KRT17 decreased osteosarcoma cell proliferation and colony formation, induced G 1 phase arrest and inhibited glycolysis in vitro. Similarly, the suppression of KRT17 decreased osteosarcoma tumor growth in vivo. Knockdown of KRT17 decreased the expression of phosphorylated (p)-AKT, p-mTOR, HIF1α and the target gene of HIF1α glucose transporter 1. Restoring the expression of p-AKT, p-mTOR or HIF1α reversed the effect of KRT17 inhibition on cell proliferation and glycolysis. These results indicated that knockdown of KRT17 may be an effective method for treating osteosarcoma through inhibiting osteosarcoma cell proliferation and the Warburg effect by suppressing the AKT/mTOR/HIF1α pathway.

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“…HIF1α is one of the downstream proteins of mTOR (33). Previous studies have demonstrated that activated mTOR can maintain the stability of HIF1α (34,35).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of KRT17 decreases osteosarcoma cell proliferation and the Warburg effect via the AKT/mTOR/HIF1α pathway

Yan

Yang

et al. 2020

Oncol Rep

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“…The presence of significant relationships between the expression and the content of the von Hippel-Lindau protein was confirmed by correlation analysis [34,35]. An increase in the VHL mRNA level is associated with decreased related protein content and expression of the transcription factor NF-κB p65.…”

Section: Discussionmentioning

confidence: 91%

“…The prevalence of the disease was accompanied by an increase in both mRNA and VHL content. p-VHL and gene expression levels in the cancers are significantly reduced compared to the adjacent untransformed tissue and correlate with the disease stage, which is especially pronounced in metastatic ccRCC [3,[29][30][31].…”

Section: Discussionmentioning

confidence: 99%

“…The presence of VHL mutations without taking into account the biological behavior of the tumor cannot determine the course, the outcome of the disease, and the effectiveness of targeted therapy [36]. The HIF overexpression associated with the p-VHL deficiency leads to cancer progression [7,[30][31]37]. Significant changes in molecular factors also determine the development of disease metastases.…”

Section: Discussionmentioning

confidence: 99%

“…An increase in tumor immunogenicity during tumor progression is the foremost progression step associated with VHL inactivation [19,20,[23][24]28]. Previous studies have revealed a relationship between VHL expression and components of the AKT/mTOR signaling cascade and transcriptional and growth factors [35], which possibly determines the response to targeted therapy. In addition, the activation of the AKT mTOR signaling pathway and an increase in gene expression and the content of transcriptional and growth factors have been shown [30][31] in ccRCC.…”

Section: Discussionmentioning

confidence: 99%

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VHL, BAP1, PBRM1, SETD2 Expression in Clear Cell Renal Carcinoma, Association With PD-1, PD-L1, PD-L2 mRNA Level

Спирина¹,

Yurnazov²,

Усынин³

et al. 2021

Preprint

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Novel mechanism of ccRCC progression is essential, including PBRM1, BAP1, and SETD2 in histone-modifying and chromatin remodeling genes. The study aimed to investigate VHL, PD-1, PD-L1, PD-L2. BAP1, PBRM1, SETD2 expression in ccRCC primary cancers and metastatic tissues associated with the cancer dissemination. A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level of VHL, PD-1, PD-L1, PD-L2. PCR in real-time performed BAP1, PBRM1, SETD2 with the previous RNA isolation. Western Blotting analysis was used for detecting the p-VHL protein content in tissues. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. ccRCC progression in VHL overexpression is associated with the decrease in BAP1 gene expression. It is revealed the heterogeneity in molecular markers in primary tumors and metastases. The low mRNA level of BAP1, PBRM1, SETD2, PD-1, PD-L1, PD-L2 in metastases compared with primary tumors were found. We show a novel mechanism for VHL tumor progression and present a new instrument and factor targeting tumor-related pathologies with p-VHL/HIF altered function.

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PI3K/Akt signaling in urological cancers: Tumorigenesis function, therapeutic potential, and therapy response regulation

Rezaei,

Nikpanjeh,

Rezaee

et al. 2023

European Journal of Pharmacology

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VHL Expression in Kidney Cancer: Relation to Metastasis Development, Transcription and Growth Factors and Component of Akt/m-TOR Signaling Pathway

Cited by 4 publications

References 13 publications

Knockdown of KRT17 decreases osteosarcoma cell proliferation and the Warburg effect via the AKT/mTOR/HIF1α pathway

Knockdown of KRT17 decreases osteosarcoma cell proliferation and the Warburg effect via the AKT/mTOR/HIF1α pathway

VHL, BAP1, PBRM1, SETD2 Expression in Clear Cell Renal Carcinoma, Association With PD-1, PD-L1, PD-L2 mRNA Level

PI3K/Akt signaling in urological cancers: Tumorigenesis function, therapeutic potential, and therapy response regulation

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