TGF-β Signaling in Gastrointestinal Cancers: Progress in Basic and Clinical Research

Yokobori, Takehiko; Nishiyama, Masahiko

doi:10.3390/jcm6010011

Cited by 33 publications

(27 citation statements)

References 66 publications

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“…Numerous known cancer-associated genes were included in the methylated gene set of the present study, certain of which are known to cause tumor development. For instance, the ectopic expression of transforming growth factor beta induced is associated with enhanced metastasis and extravasation of CRC (19)(20)(21). Polymeric immunoglobulin receptor promotes tumor growth in hepatocellular carcinoma (22), but inhibits pancreatic and periampullary adenocarcinoma development (23).…”

Section: Discussionmentioning

confidence: 99%

DNA‑methylated gene markers for colorectal cancer in TCGA database

Zhang

Sun

et al. 2020

Exp Ther Med

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Colorectal cancer (CRC) is characterized by the accumulation of genetic and epigenetic alterations in neoplastic processes. DNA methylation, as an important epigenetic process, contributes to the development of CRC. In the present study, the epigenetic landscape of genes in CRC was characterized by analyzing the dataset from The Cancer Genome Atlas database and 177 DNA-methylated genes were screened based on the criterion of the Pearson correlation (R) between expression and methylation levels being >0.4. Pathway enrichment analysis revealed prominent pathways, including transcription and metabolism, further implying their significant role in tumorigenesis. Among the methylated genes, only zinc finger protein (ZNF)726 with aberrant expression was determined to affect overall survival (OS) as well as disease-free survival of patients with CRC. In addition, ZNF726 was identified as an independent prognostic risk factor for OS in patients with CRC. The methylation-based regulation of ZNF726 expression in CRC cells was further assessed using the Cancer Cell Line Encyclopedia database. Finally, the CpG island methylation of the ZNF726 promoter was evaluated to further elucidate its role in the development of CRC. In conclusion, the epigenetic landscape of genes in terms of promoter methylation in CRC was characterized, revealing that aberrant expression of ZNF726 may be an independent prognostic risk factor for OS in patients with CRC.

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Section: Discussionmentioning

confidence: 99%

DNA‑methylated gene markers for colorectal cancer in TCGA database

Zhang

Sun

et al. 2020

Exp Ther Med

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“…TGFBI protein has been detected in most normal human tissues [229]. Although TGFBI is a downstream component of TGF-β signaling pathway, its expression is regulated not only by TGF-β, but also by other factors and mechanisms, such as autophagy [230], microRNAs [231], interleukin (IL)-1β [232], IL-4 [233], tumor necrosis factor α (TNFα) [232], cancerassociated fibroblasts (CAFs) [234], and high glucose concentrations [235,236]. TGFBI mediates cell adhesion, migration, proliferation, apoptosis, and angiogenesis through interaction with several ECM molecules (e.g.…”

Section: Transforming Growth Factor B Induced (Tgfbi) Protein and Brmentioning

confidence: 99%

Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1

Song

Sinha

et al. 2019

Oncogene

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“…(Transforming growth factor-beta-induced protein ig-h3) is marker of epithelial-to-mesenchymal transition (50) and is known to be related to cancer invasion, extravasation and dissemination (51). (Fig.…”

Section: Lamc1) Collagens (Col5a1 Col18a1) Basement Membrane Protementioning

confidence: 99%

The Impact of Oncogenic EGFRvIII on the Proteome of Extracellular Vesicles Released from Glioblastoma Cells

Choi

Montermini

Kim

et al. 2018

Molecular & Cellular Proteomics

129

133

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Epidermal growth factor receptor (EGFR)EGFR SummaryGlioblastoma multiforme (GBM) is a highly aggressive and heterogeneous form of primary brain tumors, driven by a complex repertoire of oncogenic alterations, including the constitutively active epidermal growth factor receptor (EGFRvIII). EGFRvIII impacts both cell-intrinsic and non-cell autonomous aspects of GBM progression, including cell invasion, angiogenesis and modulation of the tumor microenvironment. This is, at least in part, attributable to the release and intercellular trafficking of extracellular vesicles (EVs), heterogeneous membrane structures containing multiple bioactive macromolecules. Here we analyzed the impact of EGFRvIII on the profile of glioma EVs using isogenic tumor cell lines, in which this oncogene exhibits a strong transforming activity. We observed that EGFRvIII expression alters the expression of EV-regulating genes (vesiculome) and EV properties, including their protein composition. Using mass spectrometry, quantitative proteomic analysis and Gene Ontology terms filters, we observed that EVs released by EGFRvIIItransformed cells were enriched for extracellular exosome and focal adhesion related proteins.Among them, we validated the association of pro-invasive proteins (CD44, BSG, CD151) with EVs of EGFRvIII expressing glioma cells, and down-regulation of exosomal markers (CD81 and CD82) relative to EVs of EGFRvIII-negative cells. Nano-flow cytometry revealed that the EV output from individual glioma cell lines was highly heterogeneous, such that only a fraction of vesicles contained specific proteins. Notably, cells expressing EGFRvIII released EVs double positive for CD44/BSG, and these proteins also co-localized in cellular filopodia. We also detected the expression of homophilic adhesion molecules and increased homologous EV uptake by EGFRvIII-positive glioma cells. These results suggest that oncogenic EGFRvIII reprograms the proteome and uptake of GBM-related EVs, a notion with considerable implications for their biological activity and properties relevant for the development of EV-based cancer biomarkers.

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TGF-β Signaling in Gastrointestinal Cancers: Progress in Basic and Clinical Research

Cited by 33 publications

References 66 publications

DNA‑methylated gene markers for colorectal cancer in TCGA database

DNA‑methylated gene markers for colorectal cancer in TCGA database

Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1

The Impact of Oncogenic EGFRvIII on the Proteome of Extracellular Vesicles Released from Glioblastoma Cells

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