scholarly journals Abnormal Inflammatory Status Promotes Lymphatic Metastasis of Gallbladder Cancer Cells Through the CACUL1/NRF2/ITGBL1/ITGA9/VEGF-C Pathway

2021 ◽  
Author(s):  
Ying Kong ◽  
Kai Wang ◽  
Ai-li Suo
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Bile Acids ◽  
Inflammatory Cytokines ◽  
Lymphatic Metastasis ◽  
Chronic Infection ◽  
Poor Prognosis ◽  
Migration And Invasion ◽  
Inflammatory Status ◽  
Secondary Bile Acids

Abstract Background: Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis, but the aetiology is poorly understood. Long standing gallstone and chronic inflammation had been observed to be risk factors for GBC. Gallstone and chronic infection may lead to increased turnover of primary bile acids to secondary bile acids and inflammatory cytokines, which were known tumor promoters and might be responsible for GBC. But the exact molecular mechanism was not fully understood. Results: Our results showed that gallstones and chronic infection could increase the levels of inflammatory cytokines, and promoted the expression of CACUL1 and ITGBL1. Our study furtherly identified the highly expressed patients of CACUL1 and ITGBL1 had a poor prognosis, and them therefore might serve as a potential prognostic biomarker for GBC patients. CACUL1 promoted the expression of ITGBL1 through NRF2. Furthermore, ITGBL1 promoted the migration and invasion of GBC cells. In addition, ITGBL1 was found to induce lymphangiogenesis through the ITGA9/VEGF-C pathway and promote lymphatic metastasis. Conclusions: Our study provided new insight into GBC pathogenesis that chronic bacterial infection and gallstones leading to the production of carcinogenic precursors and inflammatory cytokines promote lymphangiogenesis and lymph node metastasis of cancer cells through CACUL1/NRF2/ITGBL1/ ITGA9/VEGF-C pathway.

Inhibition of SCAMP1 suppresses cell migration and invasion in human pancreatic and gallbladder cancer cells

Tumor Biology ◽  
2013 ◽  
Vol 34 (5) ◽  
pp. 2731-2739 ◽  
Author(s):  
Sera Yang ◽  
Kyu Taek Lee ◽  
Jin Young Lee ◽  
Jong Kyoon Lee ◽  
Kwang Hyuck Lee ◽  
...  
Keyword(s):  
Cell Migration ◽  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

scholarly journals Upregulation of LINC00659 expression predicts a poor prognosis and promotes migration and invasion of gastric cancer cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Pihai Gong ◽  
Ying Xu ◽  
Min Liu ◽  
Xiaohui Shen ◽  
Yuhang Mao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Migration And Invasion ◽  
Gastric Cancer Cells

scholarly journals Ribosome Proteins Represented by RPL27A Mark the Development and Metastasis of Triple-Negative Breast Cancer in Mouse and Human

2021 ◽  
Vol 9 ◽  
Author(s):  
Weipeng Zhao ◽  
Xichuan Li ◽  
Weiqi Nian ◽  
Jun Wang ◽  
Xiaorui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Comparative Analysis ◽  
Ribosomal Protein ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Migration And Invasion ◽  
Ribosomal Protein Genes ◽  
Gene Profiles

Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options. The lack of targeted therapies and poor prognosis of patients with TNBC have made it urgent to discover novel critical diagnosis and therapeutic targets in the TNBC field. Here, in the current study, we integrated the single-cell RNA-sequencing (scRNA-seq) data from four normal mouse mammary tissues and four mouse breast tumors. Comparative analysis was conducted to identify the gene profiles of normal epithelial cells and cancer cells at different models. Surprisingly, two ribosomal protein genes, Rpl27a and Rpl15, were significantly upregulated in the cancer cells in all the TNBC models. Next, we accessed the scRNA-seq data from human primary and metastatic TNBC tissues, and comparative analysis revealed gene profiles of human primary and metastatic TNBC cancer cells. Ribosomal protein genes, represented by RPL27A and RPL15, showed significantly upregulated expression in metastatic TNBC cancer cells. Pathway analysis on the upregulated genes of the metastatic TNBC cancer cells identified the key regulators and signaling pathways that were driving the metastasis of the TNBC cancer cells. Specifically, EIF2 signaling was significantly activated, and major member genes of this signaling pathway were upregulated. In vitro study revealed that targeting RPL27A or EIF2 signaling in a TNBC cell line, MDA-MB-231, significantly reduced cell migration and invasion. Altogether, these data suggested that the RPL27A gene is conducting critical functions in TNBC cancer development and metastasis and is a potential therapeutic target for TNBC.

scholarly journals ARHGAP11A Promotes the Malignant Progression of Gastric Cancer by Regulating the Stability of Actin Filaments through TPM1

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xiaoying Guan ◽  
Xiaoli Guan ◽  
Junjie Qin ◽  
Long Qin ◽  
Wengui Shi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Actin Filaments ◽  
Poor Prognosis ◽  
Malignant Progression ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion ◽  
The Stability

The mechanism underlying the poor prognosis of gastric cancer, including its high degree of malignancy, invasion, and metastasis, is extremely complicated. Rho GTPases are involved in the occurrence and development of a variety of malignant tumors. ARHGAP11A, in the Rho GTPase activating protein family, is highly expressed in gastric cancer, but its function and mechanism have not yet been explored. In this study, the effect of ARHGAP11A on the occurrence and development of gastric cancer and the mechanism related to this effect were studied. The expression of ARHGAP11A was increased in gastric cancer cells and tissues, and high ARHGAP11A expression in tissues was related to the degree of tumor differentiation and poor prognosis. Moreover, ARHGAP11A knockout significantly inhibited cell proliferation, cell migration, and invasion in vitro and significantly inhibited the tumorigenic ability of gastric cancer cells in nude mice in vivo. Further studies revealed that ARHGAP11A promotes the malignant progression of gastric cancer cells by interacting with TPM1 to affect cell migration and invasion and the stability of actin filaments. These results suggest that ARHGAP11A plays an important role in gastric cancer and may become a useful prognostic biomarker and therapeutic target for gastric cancer patients.

scholarly journals PD-L1 promotes tumor growth and progression by activating WIP and β-catenin signaling pathways and predicts poor prognosis in lung cancer

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Wendan Yu ◽  
Yijun Hua ◽  
Huijuan Qiu ◽  
Jiaojiao Hao ◽  
Kun Zou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Migration And Invasion

Abstract PD-L1 is overexpressed in tumor cells and contributes to cancer immunoevasion. However, the role of the tumor cell-intrinsic PD-L1 in cancers remains unknown. Here we show that PD-L1 regulates lung cancer growth and progression by targeting the WIP and β-catenin signaling. Overexpression of PD-L1 promotes tumor cell growth, migration and invasion in lung cancer cells, whereas PD-L1 knockdown has the opposite effects. We have also identified WIP as a new downstream target of PD-L1 in lung cancer. PD-L1 positively modulates the expression of WIP. Knockdown of WIP also inhibits cell viability and colony formation, whereas PD-L1 overexpression can reverse this inhibition effects. In addition, PD-L1 can upregulate β-catenin by inhibiting its degradation through PI3K/Akt signaling pathway. Moreover, we show that in lung cancer cells β-catenin can bind to the WIP promoter and activate its transcription, which can be promoted by PD-L1 overexpression. The in vivo experiments in a human lung cancer mouse model have also confirmed the PD-L1-mediated promotion of tumor growth and progression through activating the WIP and β-catenin pathways. Furthermore, we demonstrate that PD-L1 expression is positively correlated with WIP in tumor tissues of human adenocarcinoma patients and the high expression of PD-L1 and WIP predicts poor prognosis. Collectively, our results provide new insights into understanding the pro-tumorigenic role of PD-L1 and its regulatory mechanism on WIP in lung cancer, and suggest that the PD-L1/Akt/β-catenin/WIP signaling axis may be a potential therapeutic target for lung cancers.

scholarly journals A novel long non-coding RNA AC073352.1 promotes metastasis and angiogenesis via interacting with YBX1 in breast cancer

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xue Kong ◽  
Juan Li ◽  
Yanru Li ◽  
Weili Duan ◽  
Qiuchen Qi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Migration And Invasion ◽  
Breast Cancer Patients

AbstractBreast cancer is the major cause of cancer death worldwide in women. Patients with metastasis have poor prognosis and the mechanisms of breast cancer metastasis are not completely understood. Long non-coding RNAs (lncRNAs) have been shown to have crucial roles in breast cancer development and progression. However, the underlying mechanisms by which lncRNA-driven breast cancer metastasis are unknown. The main objective of this paper is to explore a functional lncRNA and its mechanisms in breast cancer. Here we identified a novel lncRNA AC073352.1 that was significantly upregulated in breast cancer tissues and was associated with advanced TNM stages and poor prognosis in breast cancer patients. In addition, AC073352.1 was found to promote the migration and invasion of breast cancer cells in vitro and enhance breast cancer metastasis in vivo. Mechanistically, we elucidated that AC073352.1 interacted with YBX1 and stabilized its protein expression. Knock down of YBX1 reduced breast cancer cell migration and invasion and could partially reverse the stimulative effects of AC073352.1 overexpressed on breast cancer metastasis. Moreover, AC073352.1 might be packaged into exosomes by binding to YBX1 in breast cancer cells resulting in angiogenesis. Collectively, our results demonstrated that AC073352.1 promoted breast cancer metastasis and angiogenesis via binding YBX1, and it could serve as a promising, novel biomarker for prognosis and a therapeutic target in breast cancer.

scholarly journals Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Youliang Wu ◽  
Delong Meng ◽  
Xin Xu ◽  
Junjun Bao ◽  
Yexiang You ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Clinical Significance ◽  
Functional Characterization ◽  
Negative Regulator ◽  
Migration And Invasion ◽  
Human Gallbladder ◽  
Normal Gallbladder ◽  
Degree Of Differentiation

Abstract Background Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines. Methods The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro. Results INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein. Conclusions These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells.

scholarly journals Long Noncoding RNA KIAA0125 Potentiates Cell Migration and Invasion in Gallbladder Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Wenjie Lv ◽  
Lei Wang ◽  
Jianhua Lu ◽  
Jiasheng Mu ◽  
Yingbin Liu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Gallbladder Cancer ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Noncoding Rnas ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Cell Migration And Invasion ◽  
Underlying Mechanisms ◽  
Insight Into

Gallbladder cancer (GBC) is one of the mostly aggressive diseases with poor prognosis due to the lack of severe symptoms. To date, little is known about the potential roles and underlying mechanisms of long noncoding RNAs (lncRNAs) in GBC initiation and progression. Thus, it provides us with a novel insight into the contribution of lncRNAs to GBC development. Remarkably, we found the differential expression of a lncRNA, namely, KIAA0125, in a pair of GBC cell sublines which possess different metastatic potentials. Then the effects of KIAA0125 on GBC cell migration, invasion, and epithelial-mesenchymal transitions (EMT) were investigated by using a lentivirus-mediated RNA interference (RNAi) system. Notably, cell migration and invasion were strongly inhibited by KIAA0125 suppression. Moreover, the expression ofβ-Catenin was increased and the expression of Vimentin was decreased in GBC-SD/M cells after KIAA0125 knockdown. Thus, our findings suggested that KIAA0125 promoted the migration and invasion of GBC cells and could serve as a potential therapeutic target in advanced GBC.

scholarly journals Overexpression of TC2N is associated with poor prognosis in gastric cancer

2020 ◽  
Author(s):  
Jianbo Xu ◽  
Xinde Ou ◽  
Jin Li ◽  
Qinbo Cai ◽  
Kaiyu Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
The Cancer Genome Atlas ◽  
Gastric Epithelium ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Term Survival

Abstract Background Tac2-N (TC2N) is a tandem C2 domain-containing protein, acting as a novel oncogene or suppressor in different kinds of cancers. However, the status of TC2N expression and its significance in gastric cancer (GC) is still unclear. The present study is aimed to elucidate the clinicopathological significance and prognostic value of TC2N level in GC. Methods We used sequencing data from the Cancer Genome Atlas (TCGA) database to analyze TC2N expression in GC by UALCAN database and Gene Expression Profiling Interactive Analysis tools (GEPIA). TC2N expression level in 12 pairs of fresh GC tissues and adjacent nontumorous tissues was detected by quantitative real-time reverse-transcription polymerase chain reaction(RT-PCR)and Western blot(WB) assays. Immunohistochemical (IHC) staining was used to detect TC2N protein expression in Paraffin-embedded tissues in our center. In vitro proliferation, migration and invasion assays were used to evaluate the effect of TC2N on functional capability of gastric cancer cells. LinkedOmics was used to identify gene expressions associated with TC2N. Results The mRNA and protein expression of TC2N in gastric cancer were both significantly higher than normal gastric mucosa. It was also elevated in gastric cancer cells compared with normal gastric epithelium cell. In vitro assays suggested that TC2N facilitated proliferation, migration and invasion of gastric cancer cells. Bioinformatic analysis showed a widespread impact of TC2N on the transcriptome and a strong interaction with tumor associated genes. We also found that TC2N was an independent prognostic factor for long-term survival in GC patients and its high expression was significantly associated with poor overall survival and recurrence-free survival. Conclusions Our results show that high level of TC2N correlates with poor prognosis in patients with gastric cancer and promotes the development of gastric cancer. Thus, TC2N expression can serve as a prognostic biomarker for patients with gastric cancer.

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