Fusobacterium nucleatum Promotes Gastric Cancer Aggressiveness through Upregulation of Cell Mobility and Interferon Genes

2020 ◽  
Author(s):  
Yung-Yu Hsieh ◽  
Shui-Yi Tung ◽  
Hung-Yu Pan ◽  
Te-Sheng Chang ◽  
Kuo-Liang Wei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Fusobacterium Nucleatum ◽  
High Multiplicity ◽  
Cancer Tissue ◽  
Multiplicity Of Infection ◽  
Continuous Increase ◽  
Cell Mobility ◽  
Cancer Aggressiveness ◽  
Tissue Specimens

Abstract Background Fusobacterium nucleatum was previously found to become a dominant species in the gastric cancer-associated microbiota of patients from Taiwan. However, the prevalence of Fusobacterium nucleatum infection in gastric cancer has not been examined in a larger patient cohort. In addition, whether Fusobacterium nucleatum elicits a cellular response in gastric cancer remains unknown.Methods A study cohort of resected gastric cancer tissue specimens was examined using nested PCR to detect Fusobacterium nucleatum. In vitro coculture of Fusobacterium nucleatum was carried out to identify the alteration in the expression profile of patient-derived gastric cancer cell line.Results approximately one-third of gastric cancer tissues are positive for Fusobacterium nucleatum. Statistical analysis showed that the risk for Fusobacterium nucleatum infection is increased in late-stage cancer tissue specimens and incurs poorer survival in Helicobacter pylori-positive patients. In vitro coculture experiment shows a drastic interferon response activated only by a high multiplicity of infection, and the response peaks within 24 hours and subsides after 72 hours of incubation. Another set of response genes is the continuous increase of actins and their regulators with prolonged time of incubation, activated by both low and high multiplicity of infection.Conclusions Our data indicates that Fusobacterium nucleatum incites an inflammatory response from the cancer cells and promotes cell mobility, likely

scholarly journals HER2, NF-κB, and SATB1 Expression Patterns in Gastric Cancer and Their Correlation with Clinical and Pathological Parameters

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Marta Smolińska ◽  
Dariusz Grzanka ◽  
Paulina Antosik ◽  
Anna Kasperska ◽  
Izabela Neska-Długosz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Statistical Significance ◽  
Expression Patterns ◽  
Clinical Information ◽  
Tissue Microarrays ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Satb1 Expression

Gastric cancer (GC) is currently recognized as one of the most common and fatal tumor worldwide. The identification of novel biomarkers in relation to clinical information as well as extending the knowledge on a multiple crosstalk between various oncogenic pathways implicated in GC carcinogenesis seems pivotal to limit the disease-associated mortality. Therefore, we assessed the expression of HER2, NF-κB, and SATB1 in a total of 104 gastric adenocarcinomas and 30 normal gastric samples and correlated the expression patterns with each other and with some clinicopathological variables. Protein expression was examined by immunohistochemistry (IHC) on tissue microarrays (TMAs), and fluorescence in situ hybridization (FISH) was employed to detect HER2 amplification. In the studied group, HER2 and SATB1 were found to be overexpressed in gastric cancer tissue in comparison to normal gastric mucosa. The expression status of the former protein was seen to differ according to some clinicopathological features, but without statistical significance, whereas the expression of the latter was not importantly associated with any of them. In turn, the NF-κB protein level was significantly related to the presence of lymph node metastasis. HER2 expression was not significantly correlated with that of other proteins, but a positive correlation was found between the expression of SATB1 and NF-κB. Further studies with a larger group of patients combined with in vitro mechanistic experiments are required to fully elucidate the role and relationship of HER2, NF-κB, and SATB1 expression in gastric cancer progression. However, to the best of our knowledge, this study is the first look at a simultaneous evaluation of these three markers in the samples of gastric cancer patients.

scholarly journals S100P is a molecular determinant of E-cadherin function in gastric cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Patrícia Carneiro ◽  
Ana Margarida Moreira ◽  
Joana Figueiredo ◽  
Rita Barros ◽  
Patrícia Oliveira ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Data Mining Approach ◽  
Molecular Determinant ◽  
Gastric Cancer Patients ◽  
And Function ◽  
E Cadherin

Abstract Background E-cadherin has been awarded a key role in the aetiology of both sporadic and hereditary forms of gastric cancer. In this study, we aimed to identify molecular interactors that influence the expression and function of E-cadherin associated to cancer. Methods A data mining approach was used to predict stomach-specific candidate genes, uncovering S100P as a key candidate. The role of S100P was evaluated through in vitro functional assays and its expression was studied in a gastric cancer tissue microarray (TMA). Results S100P was found to contribute to a cancer pathway dependent on the context of E-cadherin function. In particular, we demonstrated that S100P acts as an E-cadherin positive regulator in a wild-type E-cadherin context, and its inhibition results in decreased E-cadherin expression and function. In contrast, S100P is likely to be a pro-survival factor in gastric cancer cells with loss of functional E-cadherin, contributing to an oncogenic molecular program. Moreover, expression analysis in a gastric cancer TMA revealed that S100P expression impacts negatively among patients bearing Ecad− tumours, despite not being significantly associated with overall survival on its own. Conclusions We propose that S100P has a dual role in gastric cancer, acting as an oncogenic factor in the context of E-cadherin loss and as a tumour suppressor in a functional E-cadherin setting. The discovery of antagonist effects of S100P in different E-cadherin contexts will aid in the stratification of gastric cancer patients who may benefit from S100P-targeted therapies. Graphical abstract

scholarly journals Gastrin Vaccine Alone and in Combination With an Immune Checkpoint Antibody Inhibits Growth and Metastases of Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jill P. Smith ◽  
Hong Cao ◽  
Wenqiang Chen ◽  
Kanwal Mahmood ◽  
Teresa Phillips ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Immune Checkpoint ◽  
Receptor Expression ◽  
Tissue Array ◽  
Cancer Tissue ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

Gastric cancer is a leading cause of cancer-related deaths worldwide. Recently, clinical studies have demonstrated that many of those with advanced gastric cancer are responsive to immune checkpoint antibody therapy, although the median survival even with these new agents is less than 12 months for advanced disease. The gastrointestinal peptide gastrin has been shown to stimulate growth of gastric cancer in a paracrine and autocrine fashion through the cholecystokinin-B receptor (CCK-BR), a receptor that is expressed in at least 56.6% of human gastric cancers. In the current investigation, we studied the role of the gastrin-CCK-BR pathway in vitro and in vivo as well as the expression of the CCK-BR in a human gastric cancer tissue array. CCK-BR and PD-L1 receptor expression and gastrin peptide was found in two murine gastric cancer cells (NCC-S1 and YTN-16) by qRT-PCR and immunocytochemistry. Treatment of NCC-S1 cells with gastrin resulted in increased growth. In vivo, the effects of a cancer vaccine that targets gastrin peptide (polyclonal antibody stimulator—PAS) alone or in combination with a Programed Death-1 antibody (PD-1 Ab) was evaluated in immune competent mice (N = 40) bearing YTN-16 gastric tumors. Mice were treated with PBS, PD-1 Ab (50 µg), PAS (250 µg), or the combination of PD-1 Ab with PAS. Tumor growth was significantly slower than controls in PAS-treated mice, and tumor growth was decreased even more in combination-treated mice. There were no metastases in any of the mice treated with PAS either alone or in combination with PD-1 Ab. Tumor proliferation by the Ki67 staining was significantly decreased in mice treated with PAS monotherapy or the combination therapy. PAS monotherapy or combined with PD-1 Ab increased tumor CD8+ T-lymphocytes and decreased the number of immunosuppressive M2-polarized tumor-associated macrophages. CCK-BR expression was identified in samples from a human tissue array by immunohistochemistry confirming the clinical relevance of this study. These results confirm the significance of the gastrin-CCK-BR signaling pathway in gastric cancer and suggest that the addition of a gastrin vaccine, PAS, to therapy with an immune checkpoint antibody may decrease growth and metastases of gastric cancer by altering the tumor microenvironment.

Identification of miR-885-5p as a tumor biomarker: regulation of cellular function in cervical cancer

2021 ◽  
Author(s):  
Yuanqi Zu ◽  
Qianqian Wang ◽  
Hong Wang
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Clinical Significance ◽  
Migration And Invasion ◽  
Rank Test ◽  
Tumor Biomarker ◽  
Cancer Tissue ◽  
Cervical Cancer Cells ◽  
Tissue Specimens

Objectives: MicroRNAs were revealed as biomarkers for early detection or prognosis predictors of cancer and were involved in the progression of cancer. The present study investigated the expression pattern, potential clinical, and functional role of miR-885-5p in cervical cancer. Design: A total of 115 pairs of cervical cancer tissue specimens and adjacent non-tumor paracancerous tissue specimens were collected from the cervical cancer patients who underwent surgical resection or biopsy without preoperative systemic therapy at Maternity and Child Health Care of Zaozhuang from 2012 to 2014. Participants/Materials, Setting, Methods: The expression levels of miR-885-5p in cervical cancer were measured using the qRT-PCR assay. A follow-up study was conducted and the Kaplan-Meier method with log-rank test was used to analyze the potential clinical significance of miR-885-5p in cervical cancer. The functional experiments including CCK-8, Transwell migration, and invasion assays were used to investigate the biological function of miR-885-5p in cervical cancer cells. Results: miR-885-5p expression was decreased in tumor tissues and tumor cell lines compared to normal control. Low expression of miR-885-5p was related to lymph node metastasis, late FIGO stage, and shorter overall survival outcome. Ascending expression of miR-885-5p inhibited the proliferative, migratory, and invasive abilities of cervical cancer cells, while downregulation of miR-885-5p promoted these cellular abilities of cervical cancer cells in vitro. Limitations: The patient population size was limited, thus the clinical significance of miR-885-5p requires further verification. Secondly, the precise mechanism of miR-885-5p in cervical cancer still exclusive. In future studies, a larger sample size will be required to confirm the prognostic value of miR-885-5p in cervical cancer, and the possible targets, as well as the detailed mechanism of miR-885-5p, will be investigated. Conclusions: miR-885-5p expression was decreased in cervical cancer and downregulation of miR-885-5p promoted the progression of cervical cancer cells. miR-885-5p may be an independent prognostic predictor and therapeutic target for treating cervical cancer.

scholarly journals Upregulation of long noncoding RNA SNHG1 indicates a poor prognosis in patients with gastric cancer

2020 ◽  
Vol 18 ◽  
pp. 205873922094614
Author(s):  
Hua-Li Zhu ◽  
Jing Zou
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Expression Levels

It is indicated that the dysregulation of long noncoding RNAs (lncRNAs) is implicated in cancer progression. However, the clinical significance of lncRNA small nucleolar RNA host gene 1 (SNHG1) in gastric cancer remains elusive. The expression levels of SNHGs and the association of SNHG1/10/11 with the clinical characteristics in patients with gastric cancer were analyzed by The Cancer Genome Atlas RNA-seq data. A Cox proportional hazard regression model was used to evaluate the association of SNHG1/10/11 expression with the clinical outcomes in patients with gastric cancer. It was demonstrated that SNHG1/10/11 expression levels were dramatically elevated in gastric cancer tissue samples as compared with the adjacent normal tissues. Increased expression of SNHG1 had no correlation with the clinicopathological parameters, but acted as an independent prognostic factor of poor survival (hazard ration (HR) = 0.590, 95% confidence interval (CI) = 0.399–0.872, P = 0.008) and tumor recurrence (HR = 2.457, 95% CI = 1.442–4.186, P = 0.001) in patients with gastric cancer. In addition, knockdown of SNHG1 in vitro inhibited the proliferation and invasion of gastric cancer cells. Our findings showed that the upregulation of lncRNA SNHG1 indicated a poor prognosis in patients with gastric cancer and might offer a promising therapeutic target for gastric cancer.

scholarly journals BUBR1 Insufficiency Is Correlated with eNOS Reduction Experimentally In Vitro and In Vivo, and in Gastric Cancer Tissue

2018 ◽  
Vol 38 (11) ◽  
pp. 6099-6106 ◽  
Author(s):  
EISUKE KAWAKUBO ◽  
TAKUYA MATSUMOTO ◽  
KEIJI YOSHIYA ◽  
SHO YAMASHITA ◽  
TOMOKO JOGO ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue

Piezo1 Is as a Novel Trefoil Factor Family 1 Binding Protein that Promotes Gastric Cancer Cell Mobility In Vitro

2014 ◽  
Vol 59 (7) ◽  
pp. 1428-1435 ◽  
Author(s):  
Xiao-Ning Yang ◽  
Ya-Pi Lu ◽  
Jing-Jing Liu ◽  
Jian-Kun Huang ◽  
Yun-Peng Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Binding Protein ◽  
Trefoil Factor ◽  
Cell Mobility ◽  
Trefoil Factor Family

scholarly journals A high level of lncFGD5-AS1 inhibits epithelial-to-Mesenchymal transition by regulating the miR-196a-5p/SMAD6/BMP axis in gastric Cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Liu ◽  
Cheng Zhang ◽  
Jizhao Wang ◽  
Xu Liu ◽  
Hangying Qu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Tissue ◽  
Transformation Rate ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis

Abstract Background Long non-coding RNA (lncRNA) was a vital factor in the progression and initiation of human cancers. This study found a new lncRNA, FGD5-AS1, which can inhibit EMT process, proliferation, and metastasis in vitro and in vivo. Methods qRT-PCR was employed to test the expression of lncFGD5-AS1 in 30 gastric cancer patients’ cancer tissue and para-cancer tissue. Overexpressed lncFGD5-AS1 cells shown sharply decrease of proliferation, migration, and epithelial-mesenchymal transition (EMT). miR-196a-5p/SMAD6 was confirmed as downstream molecular mechanism of lncFGD5-AS1 by expression correlation analysis and mechanism experiments. In vivo study illustrated overexpression of lncFGD5-AS1 suppression tumor growth. Results LncFGD5-AS1 served as a ceRNA of miR-196a-5p to release its inhibition on SMAD6, a conventional inhibitor on the BMP pathway. Comparing with normal gastric cancer cells, FGD5-AS1 overexpressed group had fewer migration cells, lower cell viability, and lower EMT transformation rate. Meanwhile, xenografts nude mice injecting with overexpressed-FGD5-AS1 cells also shown smaller tumor weight and volume. Conclusion In conclusion, this research supported the first evidence that FGD5-AS1 suppressed proliferation and metastasis in gastric cancer by regulating miR-196a-5p/SMAD6/BMP axis and suggested a potential therapeutic candidate for gastric cancer.

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