Asparaginyl endopeptidase promotes the invasion and metastasis of gastric cancer through modulating epithelial-to-mesenchymal transition

Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

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Expression of Villin associated with Epithelial to Mesenchymal Transition in patients with gastric cancer relating to their clinical and morphological specifications

Asian Pacific Journal of Cancer Biology ◽

10.31557/apjcb.2020.5.1.11-14 ◽

2020 ◽

Vol 5 (1) ◽

pp. 11-14

Author(s):

Seyed Mohammad Azizi ◽

Mehrdad Hashemi ◽

Sarvenaz Falsafi ◽

Seyedeh Mina Azizi ◽

Reza Shirkoohi

Keyword(s):

Gastric Cancer ◽

Epithelial To Mesenchymal Transition ◽

Tumor Tissue ◽

Tissue Type ◽

Actin Binding ◽

Specific Cell ◽

Cross Sectional ◽

Mesenchymal Transition ◽

Biological Phenomena ◽

Two Samples

Aim and Background: Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related deaths. The metastatic invasive cells of tumor tissue are the main cause of mortality. Numerous biological phenomena are involved in organizing the metastatic process. The Epithelial to Mesenchymal Transition is one of the major mechanisms modulating malignant phenotypes by gastric epithelial cells. Specific cell signals are responsible for epithelial or mesenchymal maintenance of the cells in the tissue. These signals are evaluated by measuring the expression of epithelial and mesenchymal biomarkers in that tissue. Villin is an actin-binding protein mainly expressed in the brush border of epithelium which preserves the shape of the cell and its adhesion to the tissue. The aim of the present research is to study the expression of Villin in the cells as a feasible epithelial biomarker in order to evaluate the cross-sectional situation of the cells. Materials and Methods: 38 patients with gastric cancer that were admitted to the Cancer Institute of Imam Khomeini in a period of 6 months were chosen randomly. two samples were collected from each individual; one from the tumoral tissue and one from normal margin of the tumorous tissue. These samples were evaluated after obtaining informed consent from the patients. RNA was extracted from the samples and used as template for cDNA synthesis. The Villin expression was then measured through Real-Time PCR and statistical data according to tissue type and different grades were collected. Results: The expression of Villin in tumor tissue of the patients with gastric cancer was significantly lower than the normal tissue. Conclusion: As it appears decreased expression of Villin can act as an effective factor toward loss of epithelial nature of the cell and occurring Epithelial to Mesenchymal Transition followed by metastasis.

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Small breast epithelial mucin promotes the invasion and metastasis of breast cancer cells via promoting epithelial‑to‑mesenchymal transition

Oncology Reports ◽

10.3892/or.2020.7640 ◽

2020 ◽

Vol 44 (2) ◽

pp. 509-518

Author(s):

Qiu‑Hua Li ◽

Zhao‑Zhe Liu ◽

Ya‑Νan Ge ◽

Xing Liu ◽

Xiao‑Dong Xie ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

Small Breast ◽

Small Breast Epithelial Mucin ◽

Breast Epithelial

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SETD1A to induce epithelial-mesenchymal transition to promote invasion and metastasis through epigenetic reprogramming of snail in gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.241 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 241-241

Author(s):

Jugang Wu ◽

Jiwei Yu ◽

Yan Gu

Keyword(s):

Gastric Cancer ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Epigenetic Modification ◽

Epigenetic Reprogramming ◽

Migration And Invasion ◽

Mrna Levels ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

E Cadherin

241 Background: Aberrant epigenetic modification induces oncogenes expression and promotes cancer development. The histone lysine methyltransferase SETD1A, which specifically methylates H3K4, is involved in tumor growth and metastasis, and its ectopic expression has been detected in aggressive malignancies. Our previous study had reported that SETD1A promoted gastric cancer (GC) proliferation and tumorigenesis. However, the function and molecular mechanisms of SETD1A in GC metastasis remain to be elucidated. Methods: Transwell migration and invasion assay were performed to determine GC cell migration and invasion. Lung metastasis assay was used to detect GC cell metastasis. Western Blot and Real-time qPCR were performed to measure the protein and mRNA levels, respectively. ChIP assay was performed to investigate the methylation of H3K4. The correlation between SETD1A and EMT associated key genes in GC were performed by bioinformatic analysis. Results: In this study, we found that overexpression of SETD1A promotes GC migration and invasion, whereas knockdown of SETD1A suppressed GC migration, invasion and metastasis. Furthermore, knockdown of SETD1A suppressed GC epithelial-mesenchymal transition (EMT) by increasing the expression of epithelial marker E-cadherin, and decreasing the expression of mesenchymal markers, including N-cadherin, Fibronectin and Vimentin. Mechanistically, knockdown of SETD1A reduced the EMT key transcriptional factors snail. SETD1A was recruited to the promoter of snail, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on snail promoter. Rescue of snail restored SETD1A knockdown-induced GC migration and invasion inhibition. In addition, linear correlation between SETD1A and several key EMT genes, including E-cadherin, Fibronectin and snail, in GC specimens obtained from TCGA dataset. Conclusions: In summary, our data reveals that SETD1A mediated EMT process and induced metastasis through epigenetic reprogramming of snail.

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A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability

Cancers ◽

10.3390/cancers12071863 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1863

Author(s):

Mauricio P. Pinto ◽

Miguel Córdova-Delgado ◽

Ignacio N. Retamal ◽

Matías Muñoz-Medel ◽

M. Loreto Bravo ◽

...

Keyword(s):

Gastric Cancer ◽

Latin American ◽

Epithelial To Mesenchymal Transition ◽

Low Cost ◽

Molecular Classification ◽

The Cancer Genome Atlas ◽

Mesenchymal Transition ◽

Barr Virus ◽

Clinical Applicability ◽

Stratification System

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein–Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53−). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic

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