scholarly journals Gremlin1 Delivered by Mesenchymal Stromal Cells Promoted Epithelial-Mesenchymal Transition in Human Esophageal Squamous Cell Carcinoma

2018 ◽  
Vol 47 (5) ◽  
pp. 1785-1799 ◽  
Author(s):  
Dongxi Hong ◽  
Te Liu ◽  
Weijun Huang ◽  
Yan Liao ◽  
Lin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

Backgroud/Aims: Mesenchymal stromal cells (MSCs) are a major component of the tumor microenvironment (TME). Several studies focusing on tumor-derived MSCs have demonstrated that they exhibit a strong ability to promote the tumor epithelial-mesenchymal transition (EMT). However, the factors mediating these effects are poorly understood. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry assays were used to detect the expression of Gremlin1 (GREM1) in human esophageal squamous cell carcinoma (ESCC) tissues. ShRNA silencing, flow cytometry, cell counting kit (CCK8) assay, invasion assay, western blot were used to detect the effect of GREM1 in ECa109, TE-1 cell lines and xenograft tumor models. Results: In the current study, we found that the GREM1 was overexpressed in human ESCC tissues. The conditioned medium from mesenchymal stromal cells (MSCs-CM) enhanced the malignancy of xenograft esophageal tumors in vivo, as well as the cell proliferation, viability and invasion of the esophageal carcinoma cell lines ECa109 and TE-1 in vitro. Furthermore, the shRNA silencing of GREM1 in MSCs (shGREM1-MSCs) reversed the increased malignancy of the esophageal tumor in vivo, while the conditioned medium from shGREM1-MSCs (shGREM1-MSCs-CM) affected the cell cycle and cell invasion in vitro. These processes were accompanied by the EMT in the ECa109 and TE-1 cell lines with an alteration in the expression levels of mesenchymal and epithelial markers. Furthermore, the TGF-β/BMP (transforming growth factor-beta/bone morphogenetic protein) signaling pathway participated in the shGREM1-MSCs-CM-induced anti-tumor effect on enhanced esophageal malignancy induced by MSCs-CM treatment. Conclusions: Taken together, our study suggested that GREM1 delivered by MSCs promoted EMT in ESCC in vitro and in vivo, which is partly through TGF-β/BMP signaling pathway. The results provide experimental evidence to a potential therapeutic target in the treatment of esophageal cancer.

scholarly journals Inactivation of GSK3β and activation of NF-κB pathway via Axl represents an important mediator of tumorigenesis in esophageal squamous cell carcinoma

2015 ◽  
Vol 26 (5) ◽  
pp. 821-831 ◽  
Author(s):  
Juliano D. Paccez ◽  
Kristal Duncan ◽  
Akhona Vava ◽  
Ricardo G. Correa ◽  
Towia A. Libermann ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Glycogen Synthase ◽  
Mesenchymal Transition ◽  
Therapeutic Implications

Deregulation of Axl in esophageal squamous cell carcinoma (OSCC) with potential therapeutic implications is described for the first time. This paper also sheds light on the understanding of how Axl regulates OSCC development in vitro and in vivo. Axl expression leads to an Akt-dependent regulation of glycogen synthase kinase 3β activity and the nucluear factor kappaB (NF-κB) pathway, affecting the epithelial–mesenchymal transition.

scholarly journals Aberrant Expression and Subcellular Localization of PER2 Promote the Progression of Oral Squamous Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Fengyuan Guo ◽  
Qingming Tang ◽  
Guangjin Chen ◽  
Jiwei Sun ◽  
Junyi Zhu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Subcellular Localization ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Oral squamous cell carcinoma, one of the most prevalent cancer types in the world, has been confirmed under the influence of a key circadian gene, PER2, whose role has been identified in the development of some other types of cancers. However, the mechanism through which PER2 regulates the progress of OSCC remains largely unknown. In this study, we showed that besides the abnormal expression and subcellular localization of PER2 observed in OSCC tissues and cells as expected, these anomalous changes also existed in the adjacent noncancerous tissues, which was a novel finding in our research. The phase of PER2 rhythmic expression pattern in OSCC cells was later than that in oral keratinocytes in the protein level. In addition, we demonstrated that PER2 played as a resistant factor in the development of OSCC by upregulating TP53 and inhibiting epithelial-mesenchymal transition in vitro and in vivo. Taken together, our results identified that the development of OSCC is closely associated with PER2, the aberrant expression and subcellular localization of which facilitates the malignant progress.

scholarly journals TGIF2-Induced HMGB3 Promotes Esophageal Squamous Cell Carcinoma Progression Through TGFβ Signaling

2021 ◽  
Author(s):  
Liaoran Niu ◽  
Wanli Yang ◽  
Wei Zhou ◽  
Lili Duan ◽  
Xiaoqian Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
High Mobility ◽  
Prognostic Indicators ◽  
Proliferation And Metastasis

Abstract Background: Proliferation and metastasis are the major malignant phenotypes of esophageal squamous cell carcinoma (ESCC) and the main causes for poor survival in patients with ESCC. Nevertheless, the underlying mechanisms of ESCC proliferation and metastasis remains unclear. The high mobility group box protein family 3 (HMGB3) is one of the HMGB family members. It is critically involved in the occurrence and development of various carcinomas. However, the knowledge of HMGB3 in ESCC remains limited. In this study, we elucidated the role of HMGB3 in ESCC proliferation and metastasis, and the concrete mechanism. Methods: Expression level of HMGB3 and TGF-β interacting factor 2 (TGIF2) in ESCC cell lines and tissues was quantified by qRT-PCR, Western Blot, and immunohistochemistry. In vitro and in vivo assays revealed the functions of TGIF2 and HMGB3 in ESCC. RNA-seq was performed to search for the downstream signaling of HMGB3. ChIP assay and were performed to explore the relationship of HMGB3 and TGIF2. HMGB3-interacting protein was validated by immunoprecipitation.Results: Higher expression of TGIF2 and HMGB3 was observed in ESCC cell lines and tissues and was associated with worse prognosis of ESCC patients. TGIF2 and HMGB3 upregulation could promote ESCC proliferation and metastasis, and vice versa. TGIF2 and HMGB3 upregulation can activate Smad-dependent TGF-β signaling. TGIF2 can transcriptionally regulate HMGB3, and its TGF-β inducing capability and oncogenic role are at least partly HMGB3-dependent. Additionally, TLR3 was identified as a client protein of HMGB3, and their combination might be the reason of TGF-β activation. Conclusions: Collectively, HMGB3-dependent TGIF2 overexpression activates TGF-β signaling and promotes the proliferation and metastasis of ESCC via TLR3 regulation. These findings revealed that TGIF2 and HMGB3 could be prognostic indicators of ESCC and targeting TGIF2/HMGB3/TLR3 axis might improve the OS of ESCC patients.

scholarly journals MELK Predicts Poor Prognosis and Promotes Metastasis in Esophageal Squamous Cell Carcinoma Via Activating the NF-κB Pathway

2021 ◽  
Author(s):  
Jiecheng Ye ◽  
Wanying Deng ◽  
Ying Zhong ◽  
Hui Liu ◽  
Baoyin Guo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Biological Effects ◽  
Mesenchymal Transition ◽  
Iκb Kinase

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide with a low 5-year survival rate due to the lack of effective therapeutic strategies. Accumulating evidence has indicated that Maternal embryonic leucine zipper kinase (MELK) is highly expressed in several tumors and correlates with tumor development. However, the biological effects of MELK in ESCC are still unknown.Methods: We used data from ESCC patient tissue specimens and online datasets to evaluate differences in MELK expression between paired carcinoma. Two ESCC cell lines were selected and MELK was stably knocked down by small hairpin RNA (shRNA) of MELK. Cell phenotypical experiments and animal metastasis assays were performed to detect the influence of MELK knockdown in vitro and in vivo. The potential molecular mechanism of MELK-mediated ESCC metastasis was further investigated by Western blotting and Immunofluorescence staining.Results: In this study, the expression of MELK in human ESCC tissues was higher than that in adjacent normal tissues and was positively correlated with the poor prognosis of patients. Reducing MELK expression resulted in growth inhibition and suppression of the invasive ability of ESCC cells in vitro and in vivo. MELK inhibition induced alterations of epithelial-to-mesenchymal transition associated proteins. Mechanistically, MELK interacted with IκB kinase (IKK) and promoted the phosphorylation of IKK, by which MELK regulated activation of the NF-κB pathway.Conclusions: Collectively, our study reveals the function and mechanism of MELK in the cell metastasis of ESCC, which may be a potential therapeutic target for ESCC.

scholarly journals LncRNA SNHG17 regulates cell proliferation and invasion by targeting miR-338-3p/SOX4 axis in esophageal squamous cell carcinoma

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Wenhu Chen ◽  
Lifang Wang ◽  
Xiaoyan Li ◽  
Changan Zhao ◽  
Liang Shi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Software Analysis

AbstractSmall nucleolar RNA host gene 17 (SNHG17), a novel functional long noncoding RNA, has been demonstrated to play an essential role in the oncogenesis of several tumors. However, for esophageal squamous cell carcinoma (ESCC) the expression pattern and detailed function of SNHG17 are largely unknown. Hence, we conducted this study to explore potential roles and underlying oncogenic mechanisms for SNHG17 in ESCC progression. Results demonstrated SNHG17 to be markedly upregulated in ESCC. Knockdown of SNHG17 significantly suppressed ESCC cell proliferation, invasion, and epithelial–mesenchymal transition in vitro and tumor growth in vivo. Online database software analysis found miR-338-3p to interact with SNHG17 with the level of miR-338-3p negatively correlated with SNHG17 levels in ESCC samples. Further, miR-338-3p was found to directly target SRY-box transcription factor 4 (SOX4) in ESCC cells. Mechanistic analysis suggested that SNHG17 acts as an endogenous “sponge” competing with miR-338-3p to regulate SOX4, thereby promoting tumor progression. These results suggest that these molecular interactions may be potential therapeutic targets for ESCC.

scholarly journals FAP overexpression induce Epithelial-Mesenchymal Transition (EMT) in oral squamous cell carcinoma by down-regulating DPP9 gene

2019 ◽  
Author(s):  
Qing-qing Wu ◽  
Meng Zhao ◽  
Guang-zhao Huang ◽  
Ze-nan Zheng ◽  
Wei-sen Zeng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Promoter ◽  
Tissue Samples ◽  
Mesenchymal Transition

AbstractFAP acts as a tumor promoter via epithelial-mesenchymal transition (EMT) in human oral squamous cell carcinoma (OSCC). The present study was designed to investigate the interaction proteins with FAP and explore the precise mechanism of FAP promoting EMT in OSCC. IP-MS analysis confirmed that DPP9 was an interacting protein of FAP. DPP9 was down-regulated in OSCC tissue samples compared with MNT using immunohistochemistry and quantitative-PCR detection. Lower DPP9 was correlated with unfavorable overall survival of patients with OSCC. Repressing DPP9 accelerates the proliferation of OSCC cells in vitro and in vivo. Mechanistically, overexpression of FAP downregulate the expression of the DPP9 and the effect of FAP on OSCC proliferation, migration, invasion and EMT could be reversed by up-regulated DPP9. Our study suggests that FAP could induce EMT and promote carcinogenesis in oral squamous cell carcinoma by down-regulating DPP9 gene. That will hint different dimension on therapy for patients with OSCC.

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