Rab5 regulates the proliferation, migration and invasion of glioma cells via cyclin E

Zhao, Jian; Zhang, Lianglong; Jin, Liang; Lan, Weitu; Zhang, Wei; Gao, Guiyan

doi:10.3892/ol.2020.11660

Cited by 8 publications

(6 citation statements)

References 31 publications

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“…TBC1D3H belongs to TBC1 domain family, which can act as a GTPase activating protein for RAB5 ( Itoh et al, 2006 ; UniProt, 2021 ). Its dysregulation can lead to tumorigenesis ( Jian et al, 2020 ). Other proteins with TBC1 domain also function in cancer; for instance, TBC1 domain family member 23 can interact with Ras-related protein Rab-11A to promote poor prognosis in lung cancer ( Zhang et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of DNA 5-Methylcytosine and N6-Adenine Methylation by Nanopore Sequencing in Hepatocellular Carcinoma

Zhang

Rong

et al. 2022

Front. Cell Dev. Biol.

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DNA methylation is a widespread epigenetic signal in human genome. With Nanopore technology, differential methylation modifications including 5-methylcytosine (5mC) and 6-methyladenine (6mA) can be identified. 5mC is the most important modification in mammals, although 6mA may also function in growth and development as well as in pathogenesis. While the role of 5mC at CpG islands in promoter regions associated with transcriptional regulation has been well studied, but the relationship between 6mA and transcription is still unclear. Thus, we collected two pairs of tumor tissues and adjacent normal tissues from hepatocellular carcinoma (HCC) surgical samples for Nanopore sequencing and transcriptome sequencing. It was found that 2,373 genes had both 5mC and 6mA, along with up- and down-regulated methylation sites. These genes were regarded as unstable methylation genes. Compared with 6mA, 5mC had more inclined distribution of unstable methylation sites. Chi-square test showed that the levels of 5mC were consistent with both up- and down-regulated genes, but 6mA was not significant. Moreover, the top three unstable methylation genes, TBC1D3H, CSMD1, and ROBO2, were all related to cancer. Transcriptome and survival analyses revealed four potential tumor suppressor genes including KCNIP4, CACNA1C, PACRG, and ST6GALNAC3. In this study, we firstly proposed to combine 5mC and 6mA methylation sites to explore functional genes, and further research found top of these unstable methylation genes might be functional and some of them could serve as potential tumor suppressor genes. Our study provided a new solution for epigenetic regulation research and therapy of HCC.

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Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of DNA 5-Methylcytosine and N6-Adenine Methylation by Nanopore Sequencing in Hepatocellular Carcinoma

Zhang

Rong

et al. 2022

Front. Cell Dev. Biol.

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“…These observations suggest a mechanism that the Rab5-GEF, Rabex-5, is recruited to the TGN by GGAs and promotes cargo transport from the TGN to the early endosome via GGA vesicles. Human Rab5 and Rabex-5 have been reported to be upregulated and promote the metastasis ability in several types of malignant tumor cells (Jian et al, 2020; Wang et al, 2014). Intriguingly, mammalian RAB11, ARF1, and PI4KIIIβ (homologues for Arf1p, Rab11 and Pik1p) are also upregulated in these tumor cells (Ferro et al, 2021; Gu et al, 2017; Morrow et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Distinct role of TGN-resident clathrin adaptors for Rab5 activation in the TGN-endosome trafficking pathway

Nagano

Aoshima

Shimamura

et al. 2023

Preprint

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Clathrin-mediated vesicle trafficking plays central roles in the post-Golgi transport pathways from the trans-Golgi network (TGN) to endosomes. In yeast, two clathrin adaptors - AP-1 complex and GGA proteins (GGAs) - are predicted to generate distinct transport vesicles at the TGN, and epsin-related Ent3p/Ent5p act as accessories for these adaptors. Recently, we showed that vesicle transport from the TGN, rather than from the plasma membrane, is crucial for Rab5-mediated endosome formation, and that Ent3p/5p are crucial for this process, whereas AP-1 and GGAs are dispensable. However, these observations were incompatible with previous studies showing that these adaptors are required for Ent3p/5p recruitment to the TGN, and thus the overall mechanism responsible for regulation of Rab5 activity remains ambiguous. Here we investigated the functional relationships between clathrin adaptors in post-Golgi-mediated Rab5 activation. We were able to show that AP-1 disruption in ENT3/ENT5-deleted mutant impairs Rab5-GEF Vps9p transport to the Rab5 compartment, and severely reduces Rab5 activity. Additionally, GGAs, Golgi-resident PI4 kinase Pik1p and Rab11 GTPases Ypt31p/32p were found to have partially overlapping functions for recruitment of AP-1 and Ent3p/5p to the TGN. These findings suggest a distinct role of clathrin adaptors for Rab5 activation in the TGN-endosome trafficking pathway.

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“…The role of Rab5 in glioma progression and resistance to anti-EGFR therapy is still a matter of debate. Indeed, a recent study reported that in humans, Rab5 is overexpressed in glioma tissue compared to normal brain and that overexpression of Rab5 leads to enhanced proliferation and migration, which can be reversed by knockout of Rab5 [48]. By contrast, it has been shown that Rab5 inhibition sustains aberrant oncogenic EGFR signalling.…”

Section: Discussionmentioning

confidence: 99%

Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells

Silva

Choulier

Thevenard-Devy

et al. 2021

Cells

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EGFR (epidermal growth factor receptor), a member of the ErbB tyrosine kinase receptor family, is a clinical therapeutic target in numerous solid tumours. EGFR overexpression in glioblastoma (GBM) drives cell invasion and tumour progression. However, clinical trials were disappointing, and a molecular basis to explain these poor results is still missing. EGFR endocytosis and membrane trafficking, which tightly regulate EGFR oncosignaling, are often dysregulated in glioma. In a previous work, we showed that EGFR tyrosine kinase inhibitors, such as gefitinib, lead to enhanced EGFR endocytosis into fused early endosomes. Here, using pharmacological inhibitors, siRNA-mediated silencing, or expression of mutant proteins, we showed that dynamin 2 (DNM2), the small GTPase Rab5 and the endocytosis receptor LDL receptor-related protein 1 (LRP-1), contribute significantly to gefitinib-mediated EGFR endocytosis in glioma cells. Importantly, we showed that inhibition of DNM2 or LRP-1 also decreased glioma cell responsiveness to gefitinib during cell evasion from tumour spheroids. By highlighting the contribution of endocytosis proteins in the activity of gefitinib on glioma cells, this study suggests that endocytosis and membrane trafficking might be an attractive therapeutic target to improve GBM treatment.

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Rab5 regulates the proliferation, migration and invasion of glioma cells via cyclin E

Cited by 8 publications

References 31 publications

Comprehensive Analysis of DNA 5-Methylcytosine and N6-Adenine Methylation by Nanopore Sequencing in Hepatocellular Carcinoma

Comprehensive Analysis of DNA 5-Methylcytosine and N6-Adenine Methylation by Nanopore Sequencing in Hepatocellular Carcinoma

Distinct role of TGN-resident clathrin adaptors for Rab5 activation in the TGN-endosome trafficking pathway

Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells

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