Gastric Cancer Migration Research Articles

LncRNA MBNL1-AS1 represses gastric cancer progression via the TGF-β pathway by modulating miR-424-5p/Smad7 axis

ABSTRACT Studies over the past decades have implicated lncRNAs in promoting the development, migration and invasion of gastric cancer (GC). However, the role and mechanism of lncRNA MBNL1-AS1 in GC promotion are poorly understood. In this research, qRT-PCR showed that MBNL1-AS1 was down-regulated in GC tissues and cells. Cell experiments and the animal study demonstrated that MBNL1-AS1 knockdown accelerated GC cell proliferation, migration, and invasion, thus restraining cell apoptosis. Meanwhile, overexpression of MBNL1-AS1 repressed GC cell promotion. Bioinformatics analysis confirmed that MBNL1-AS1 binds to miR-424-5p via negative modulation. Rescue experiments showed that decreased miR-424-5p level inhibited GC cell promotion by silencing MBNL1-AS1. Furthermore, Smad7 was identified as a target of miR-424-5p that could reverse the promotion of GC cell growth mediated by miR-424-5p. Western blot results proved that MBNL1-AS1 affected TGF-β/SMAD pathways by regulating the miR-424-5p/Smad7 axis. Collectively, MBNL1-AS1 restrained GC growth via the miR-424-5p/Smad7 axis and thus could be a promising target for GC therapy. These findings illustrate that lncRNA MBNL1-AS1, as a tumor suppressor gene, participates in GC progression by regulating miR-424-5p/Smad7 axis, thus activating TGF-β/EMT pathways. The evidence may provide a potential marker for GC patients.

The SKA3-DUSP2 Axis Promotes Gastric Cancer Tumorigenesis and Epithelial-Mesenchymal Transition by Activating the MAPK/ERK Pathway

Background: Spindle and kinetochore-related complex subunit 3 (SKA3), a member of the SKA family of proteins, is associated with the progression of multiple cancers. However, the role of SKA3 in gastric cancer has not been studied. Methods: The expression levels of SKA3 and dual-specificity phosphatase 2 (DUSP2) proteins were detected by immunohistochemistry. The effects of SKA3 and DUSP2 on the proliferation, migration, invasion, adhesion, and epithelial-mesenchymal transition of gastric cancer were studied in vitro and in vivo. Results: Immunohistochemical analysis of 164 cases of gastric cancer revealed that high expression of SKA3 was negatively correlated with DUSP2 expression and related to N stage, peritoneal metastasis, and poor prognosis. In vitro studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. In vivo experiments showed that silencing SKA3 inhibited tumor growth and peritoneal metastasis. Mechanistically, SKA3 negative regulates the tumor suppressor DUSP2 and activates the MAPK/ERK pathway to promote gastric cancer. Conclusion: Our results indicate that the SKA3-DUSP2-ERK1/2 axis is involved in the regulation of gastric cancer progression, and SKA3 is a potential therapeutic target for gastric cancer.

MicroRNA-200b-3p restrains gastric cancer cell proliferation, migration, and invasion via C-X-C motif chemokine ligand 12/CXC chemokine receptor 7 axis

ABSTRACT This study was conducted to investigate the impact of microRNA (miR)-200b-3p on viability, migration, and invasion of gastric cancer (GC) cells and its mechanism. Quantitative real-time PCR (qRT-PCR) was conducted to measure miR-200b-3p expression in GC tissues and cells; besides, the relationship between miR-200b-3p expression and overall survival time (OS) was analyzed with OncomiR database; cell counting kit-8 (CCK-8), colony formation assay, flow cytometry, scratch healing assay, and Transwell assay were performed to detect the proliferation, cell cycle progression, migration, and invasion of GC cells; a lung metastasis model in nude mice was used to examine the effect of miR-200b-3p on the metastasis of GC cells in vivo; the interplay between miR-200b-3p and C-X-C motif chemokine ligand 12 (CXCL12) mRNA 3’ UTR was predicted by bioinformatics and verified with a dual-luciferase reporter gene assay; besides, the expression of CXCL12 and CXC chemokine receptor 7 (CXCR7) was probed by Western blot. It was found that miR-200b-3p expression was down-regulated in GC tissues, which was remarkably associated with the lymph node metastasis and decrease of differentiation of GC; transfection with miR-200b-3p mimics restrained the growth, migration, and invasion of GC cells in vitro, induced cell cycle arrest, and inhibited CXCL12 and CXCR7 expression levels; transfection of miR-200b-3p inhibitors worked oppositely in vitro and promoted lung metastasis in vivo. CXCL12 was confirmed as the downstream target of miR-200b-3p and was negatively modulated by miR-200b-3p. In conclusion, miR-200b-3p inhibited GC progression via regulating CXCL12/CXCR7 axis.

Docetaxel and 5-FU enhanced the inhibitory effects of apatinib and ramucirumab on growth and migration of gastric cancer

BackgroundGastric cancer (GC) is one of the most common malignant tumors in the world. The clinical benefit of anti-angiogenic strategy as a single drug is limited. Some studies showed that the combination of anti-angiogenic therapy and chemotherapy exhibited synergistic effect and reduced the side effects of chemotherapy drugs. We investigated the combined effects of these two types of drugs in gastric cancer cells in vitro and in vivo. Methodscell viability, migration, invasion, and apoptosis were evaluated by CCK-8, wound-healing, transwell, and Annexin V-FITC/PI assay, respectively. In vivo anti-cancer efficacy was tested for the cell proliferation and metastasis in cell line derived tumor xenograft (CDX) model and patient derived tumor xenografted (PDX) model based on Tg (fli-1: EGFP) zebrafish embryos; ResultsIn the cell experiments, the combination of the two types of drugs could inhibit the proliferation and metastasis of gastric cancer cells and promote apoptosis through VEGFR-2/AKT/ERK1/2 signal. In the zebrafish CDX (zCDX) model and zebrafish PDX (zPDX) model, the combination of the two treatment also showed a synergistic effect in inhibiting gastric cancer cell metastasis and cell proliferation. ConclusionsApatinib/ramucirumab targeted therapy combined with docetaxel or 5-fluorouracil (5-FU) may serve as an effective treatment strategy for patients with advanced gastric cancer.

Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression

ObjectivesZiyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. MethodsTargets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. ResultsThe network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. ConclusionZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.

The E3 ubiquitin ligase, FBXW5, promotes the migration and invasion of gastric cancer through the dysregulation of the Hippo pathway

F-box and WD repeat domain-containing 5 (FBXW5), with WD40 repeats, can bind to the PPxY sequence of the large tumor suppressor kinases 1/2 (LATS1/2) kinase domain, resulting in ubiquitination. Ubiquitination and the subsequent degradation of LATS1/2 abrogate the Hippo pathway and worsen gastric cancer (GC). However, the effects and molecular mechanisms of FBXW5 in GC remain unexplored. To elucidate the clinical significance of FBXW5, immunohistochemistry was conducted to reveal the positive correlation between FBXW5 expression and lymph node metastasis (p < 0.001) and TNM stage (training cohort: p = 0.018; validation cohort: p = 0.001). Further, patients with high FBXW5 expression were found to have poor prognosis (training cohort: log-rank p = 0.020; validation cohort: log-rank p = 0.025). Cell experiments revealed the promoting effects of FBXW5 on the proliferation, invasion, metastasis, and chemoresistance of GC cells. Blocking LATS1-YAP1 leads to the loss of FBXW5-mediated regulation of the Hippo pathway and partial functions. Further, co-immunoprecipitation and in vivo ubiquitination assays revealed the interaction between FBXW5 and LATS1, which promoted the ubiquitination and degradation of LATS1. Based on mouse xenograft assays, FBXW5 silencing attenuated the growth of subcutaneous tumor xenografts. Altogether, FBXW5 was found to inactivate the Hippo signaling pathway by enhancing LATS1 ubiquitination and degradation, which promoted the invasion, metastasis, and drug resistance of GC cells.

Ferroptosis‑related long non‑coding RNAs and the roles of LASTR in stomach adenocarcinoma.

Ferroptosis is a form of programmed cell death that participates in diverse physiological processes. Increasing evidence suggests that long noncoding RNAs (lncRNAs) regulate ferroptosis in tumors, including stomach adenocarcinoma (STAD). In the present study, RNA-sequencing data from The Cancer Genome Atlas database and ferroptosis-related markers from the FerrDb data resource were analyzed to select differentially expressed lncRNAs. Univariate and multivariate Cox regression analyses were performed on these differentially expressed lncRNAs to screen 12 lncRNAs linked with overall survival (OS) and 13 associated with progression-free survival (PFS). Subsequently, two signatures for predicting OS and PFS were established based on these lncRNAs. Kaplan-Meier analyses indicated that the high-risk group of patients with STAD had relatively poor prognosis. The areas under the receiver operating characteristic curves of the two signatures indicated their excellent efficacy in predicting STAD prognosis. In addition, the effect of the lncRNA LASTR on proliferation and migration in gastric cancer was confirmed and the relationship between LASTR and ferroptosis was initially explored through experiments. These results provide potential novel targets for tumor treatment and promote personalized medicine.

ASO Visual Abstract: TRPV2 Promotes Cell Migration and Invasion in Gastric Cancer via the TGF-β-Signaling Pathway

ASO Visual Abstract: TRPV2 Promotes Cell Migration and Invasion in Gastric Cancer via the TGF-β-Signaling Pathway

P53-Induced LINC00893 Regulates RBFOX2 Stability to Suppress Gastric Cancer Progression.

Long noncoding RNAs (lncRNAs) have been reported to regulate diverse tumorigenic processes. However, little is known about long intergenic non-protein coding RNA 00893 (LINC00893) and its role in gastric cancer (GC). Herein we investigated its biological functions and molecular mechanism in GC. LINC00893 was decreased in GC tissues but significantly elevated in AGS cells after treatment with Nutlin-3. In GC patients, it was found that low expression of LINC00893 was correlated with tumor growth, metastasis and poor survival. Functionally, overexpression of LINC00893 suppressed the proliferation, migration and invasion of GC cells. Mechanistically, LINC00893 regulated the expression of epithelial-mesenchymal transition (EMT)-related proteins by binding to RNA binding fox-1 homolog 2 (RBFOX2) and promoting its ubiquitin-mediated degradation, thus suppressing the EMT and related functions of GC. In addition, the transcription factor p53 can regulate the expression of LINC00893 in an indirect way. Taken together, these results suggested that LINC00893 regulated by p53 repressed GC proliferation, migration and invasion by functioning as a binding site for RBFOX2 to regulate its stability and the expression of EMT-related proteins. LINC00893 acts as a tumor-inhibiting lncRNA that is induced by p53 in GC and regulates EMT by binding to RBFOX2, thus providing a novel experimental basis for the clinical treatment of GC.

Erianin Regulates PI3K/AKT Signaling Pathway and Inhibits Cell Invasion and Migration in Gastric Cancer In Vitro

Gastric carcinoma is one of the most malignant cancers associated with lifestyle and genetics. The currently used pharmacotherapeutics are associated with serious side effects necessitating a need for safer drugs. Erianin is a natural plant bioactive substance known for its anti-cancerous and a variety of other biologic activities. Using a variety of measures such as colony formation, invasion and migration assay, and flow cytometry and apoptosis, we have examined the effect of erianin on human gastric adenocarcinoma cells representing gastric carcinoma. The results show that erianin ensured (i) inhibition of proliferation, invasion, and migration capabilities, (ii) induction of apoptosis, and (iii) inhibition of the activation of phosphatidylinositol 3-kinase/Protein kinase B signaling pathway. In conclusion, these results show a potential for erianin in the management of gastric carcinoma.

MT1G inhibits the growth and epithelial-mesenchymal transition of gastric cancer cells by regulating the PI3K/AKT signaling pathway.

Gastric carcinoma (GC) is a malignant tumor that has high mortality and morbidity worldwide. Although many efforts have been focused on the development and progression of GC, the underlying functional regulatory mechanism of GC needs more clarification. Metallothionein 1G (MT1G) is a member of the metallothionein family (MTs), and hypermethylation of MT1G occurred in a variety of cancers, including gastric cancer. However, the functional mechanism of MT1G in GC remains unclear. Here, we demonstrated that MT1G was down-regulated in GC tissues and cells. Overexpression of MT1G inhibited cell proliferation, foci formation and cell invasion, while knockdown of MT1G increased cell proliferation, foci formation and cell invasion. In addition, MT1G overexpression inhibited cell cycle progression and MT1G deficiency exerted opposite phenotype. p-AKT was negatively regulated by MT1G. In summary, our study reveals that MT1G exerts crucial role in regulating of cell proliferation and migration of gastric cancer, providing new insights for MT1G-related pathogenesis and a basis for developing new strategies for treatment of GC.

Green walnut husk extracts Proliferation and Migration in Gastric Cancer.

Background: In the past few decades, natural products have become an increasingly important source of potential anti-cancer agents. The green walnut husk(GWH) extracts have been reported to inhibit multiple tumor cells and might be a promising chemopreventive agent in human neoplasia. However, it is not clear whether GWH extracts inhibit gastric cancer.Methods: Proliferation, invasion, and migration of gastric cancer cells were assessed by the CCK-8, wound-healing, and Transwell assay. The apoptotic rate was detected by flow cytometry(FCM). The expressions of Bcl-2, Bax, and Caspase-3 proteins were examined by Western blot. Moreover, the growth of gastric cancer cells was assessed using orthotopic xenograft models, and related proteins expressions were evaluated using immunohistochemistry. Finally, the Gene expression profile of gastric cancer treated with GWH extracts was evaluated by using High-throughput RNA sequencing(RNA-seq).Results: GWH extracts effectively inhibited gastric cancer cell growth in vitro and in vivo. In vivo, GWH extracts inhibited the survival of gastric cancer cells in a dose and time-dependent manner, inhibited the migration and invasion of gastric cancer cells, regulated the expressions of apoptosis-related proteins, and induced apoptosis of gastric cancer cells. In vitro, GWH extracts inhibited the growth of mouse xenografted tumors. A total of differentially expressed genes, of which 41 genes were up-regulated, and 610 genes were down-regulated, were identified by RNA-seq. GO, and KEGG analysis showed that these differentially expressed genes might be related to the mechanism of the anti-gastric cancer effect of GWH extracts.Conclusion: GWH extracts played an anti-gastric cancer effect by inducing apoptosis and inhibiting invasion. Secondly, the differential expression of many genes, multiple signal pathways, and metabolic pathways in gastric cancer play an essential role in the anti-gastric cancer effect of GWH extracts. The results suggested that GWH extracts are expected to be a low toxic drug for the treatment of gastric cancer in the future.

Research Progress of ANP, NPRA, and Cx43 in Gastric Cancer

The occurrence and development of gastric cancer are regulated by many factors and result from the joint action of many factors. Studies have shown that ANP, NPRA, and Cx43 play a vital role in the proliferation and migration of gastric cancer. This article reviews the relationship between Atrial natriuretic peptide (ANP), Atrial natriuretic peptide receptor A (NPRA), and Connexin43 (Cx43) with the occurrence and development of gastric cancer. The review aims to provide an effective reference value for scientific research and clinical treatment.

CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment.

Little is known about the oncogenic role or biological function of copine Ⅷ (CPNE8) in gastric cancer (GC). Based on TCGA database, we screened for CPNE8 and analyzed the expression of CPNE8 in GC. The correlations between CPNE8 and clinical features were analyzed using TCGA and GEO databases. The prognostic value of CPNE8 was assessed using Cox analysis and Kaplan-Meier curves. The results showed that increased expression of CPNE8 was positively correlated with metastasis and can be considered an independent prognostic risk factor for poor survival. We found that CPNE8 can promote cell proliferation, migration, and invasiveness in GC using in vitro and in vivo experiments. Our study demonstrated that CPNE8 promotes tumor progression via regulation of focal adhesion, and these effects can be rescued by focal adhesion kinase (FAK) inhibitor GSK2256098 or knockdown of FAK. In addition, CPNE8 was correlated significantly with the infiltration of cancer-associated fibroblasts and immune cells, as demonstrated by various algorithms, and high CPNE8 expression predicted poor efficacy of immune checkpoint therapy. Our findings suggest that CPNE8 modulates focal adhesion and tumor microenvironment to promote GC progression and invasiveness and could serve as a novel prognostic biomarker in GC.

RETRACTED ARTICLE: Long non-coding RNA CCL2 promoted gastric cancer function via miR-128/ PARP2 signal pathway

Statement of Retraction Liang Ma, Yunshan Jiang, Ning Wu. 2022. Long non-coding RNA CCL2 promoted gastric cancer function via miR-128/ PARP2 signal pathway - 2022, Long non-coding RNA CCL2 promoted gastric cancer function via miR-128/ PARP2 signal pathway, Bioengineered 13(1), doi: 10.1080/21655979.2021.2020548 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. All authors listed in this publication have been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

MiR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway

miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway

TULP3 silencing suppresses cell proliferation, migration and invasion in gastric cancer via the PTEN/Akt/Snail pathway

BackgroundTubby-like protein 3 (TULP3) is a member of the tubby family, has been related to the development of nervous system by gene knockout researches. Nevertheless, the role of TULP3 in the gastric cancer is not clear. MethodsWestern blotting and real-time polymerase chain reaction (PCR) were employed for the quantitative detection of TULP3 expression in the gastric cancer and consecutive non-cancerous tissues, and gastric cancer cells. The roles of TULP3 in invasion, migration as well as proliferation of the gastric cancer cell in vivo and in vitro through utilizing colony formation, MTT, wound-healing, transwell and mouse xenograft model. Western blotting assay was implemented in order to clarify the potential molecular mechanisms. Furthermore, electron microscopy and western blot were evaluated TULP3 expression in gastric cancer patient extracted serum exosomes. ResultsTULP3 expression levels were remarkably upregulated in the gastric cancer tissues and cells. Subsequent functional assays demonstrated that TULP3 downregulation suppressed invasion, migration as well as the proliferation of the gastric cancer cell. Mechanism assays depicted that the PTEN/Akt/Snail signaling pathway can inhibit invasion, migration as well as the proliferation of the gastric cancer cell via TULP3 silencing. Finally, we found that the expression of TULP3 could be determined in the extracted serum exosomes. The expression of TULP3 in gastric cancer group was higher in comparison with normal group. ConclusionsOur results reveal that TULP3 might serve as a potential prognostic biomarker and therapeutic target for the treatment of gastric cancer.

TP73-AS1 promotes gastric cancer proliferation and invasion by regulation miR-27b-3p/TMED5 axis.

Background: Gastric cancer (GC) is a common gastrointestinal malignancy. Evidence suggests that long non-coding RNAs (lncRNAs) influence mRNA expression to induce GC progression. We aim to investigate the function and regulatory mechanism of TP73-AS1 in GC.Materials and methods: We detected TP73-AS1, miR-27b-3p, and TMED5 (Transmembrane P24 Trafficking Protein 5) by real-time polymerase chain reaction (RT-PCR). Similarly, the protein levels of TMED5 and wnt/β-catenin were detected by western-blot. The colony formation and Cell-Counting Kit-8 (CCK-8) assay detected cell proliferation. Transwell and scrape assay tested cell migration and invasion. Dual-luciferase reporter assays confirmed directed binding targets. Tumor xenograft in nude mice checked the result in vivo.Results: TP73-AS1 over-expressed in GC. Suppressed TP73-AS1 inhibited cell proliferation, migration, and invasion. However, down-regulated miR-27b-3p could reverse the effects of weakenTP73-AS1 on the progression of GC. Moreover, TMED5 was also up-regulated in GC. Both TP73-AS1 and TMED5 were the direct target of miR-27b-3p. Meanwhile, miR-27b-3p was a negative correlation with TP73-AS1 and TMED5. The TP73-AS1/miR-27b-3p/TMED5 axis regulate wnt/β-catenin pathway.Conclusion: TP73-AS1 promoted GC proliferation, migration, and invasion by sponging miR-27b-3p to regulate TMED5. TP73-AS1 was a potential onco-lncRNA in GC.

Targeting histone deacetylase-3 blocked epithelial-mesenchymal plasticity and metastatic dissemination in gastric cancer

Background and purposeHistone deacetylase (HDAC) inhibitors (HDIs) can modulate the epithelial-mesenchymal transition (EMT) progression and inhibit the migration and invasion of cancer cells. Emerging as a novel class of anti-cancer drugs, HDIs are attracted much attention in the field of drug discovery. This study aimed to discern the underlying mechanisms of Honokiol in preventing the metastatic dissemination of gastric cancer cells by inhibiting HDAC3 activity/expression.Experimental approachClinical pathological analysis was performed to determine the relationship between HDAC3 and tumor progression. The effects of Honokiol on pharmacological characterization, functional, transcriptional activities, organelle structure changes, and molecular signaling were analyzed using binding assays, differential scanning calorimetry, luciferase reporter assay, HDAC3 activity, ER stress response element activity, transmission electron microscopy, immune-blotting, and Wnt/β-catenin activity assays. The in vivo effects of Honokiol on peritoneal dissemination were determined by a mouse model and detected by PET/CT tomography.Key resultsHDAC3 over-expression was correlated with poor prognosis. Honokiol significantly abolished HDAC3 activity (Y298) via inhibition of NFκBp65/CEBPβ signaling, which could be reversed by the over-expression of plasmids of NFκBp65/CEBPβ. Treatments with 4-phenylbutyric acid (a chemical chaperone) and calpain-2 gene silencing inhibited Honokiol-inhibited NFκBp65/CEBPβ activation. Honokiol increased ER stress markers and inhibited EMT-associated epithelial markers, but decreased Wnt/β-catenin activity. Suppression of HDAC3 by both Honokiol and HDAC3 gene silencing decreased cell migration and invasion in vitro and metastasis in vivo.Conclusions and implicationsHonokiol acts by suppressing HDAC3-mediated EMT and metastatic signaling. By prohibiting HDAC3, metastatic dissemination of gastric cancer may be blocked.Graphical abstractConceptual model showing the working hypothesis on the interaction among Honokiol, HDAC3, and ER stress in the peritoneal dissemination of gastric cancer. Honokiol targeting HDAC3 by ER stress cascade and mitigating the peritoneal spread of gastric cancer. Honokiol-induced ER stress–activated calpain activity targeted HDAC3 and blocked Tyr298 phosphorylation, subsequently blocked cooperating with EMT transcription factors and cancer progression. The present study provides evidence to demonstrate that HDAC3 is a positive regulator of EMT and metastatic growth of gastric cancer cells. The findings here imply that overexpressed HDAC3 is a potential therapeutic target for honokiol to reverse EMT and prevent gastric cancer migration, invasion, and metastatic dissemination.• Honokiol significantly abolished HDAC3 activity on catalytic tyrosine 298 residue site. In addition, Honokiol-induced ER stress markedly inhibited HDAC3 expression via inhibition of NFκBp65/CEBPβ signaling.• HDAC3, which is a positive regulator of metastatic gastric cancer cell growth, can be significantly inhibited by Honokiol.• Opportunities for HDAC3 inhibition may be a potential therapeutic target for preventing gastric cancer metastatic dissemination.

SATB1 enhances gastric cancer progression and metastasis via upregulation of CLIP4/DZIP1/ PRICKLE2 axis in gastric cancer patients

SATB1 (Special AT-rich sequence binding protein 1) plays key role in chromatin remodeling and geneexpression. SATB1 has been shown to promote invasion, migration and metastasis. However, the underlying molecular mechanisms, function and clinicopathological features of SATB1 in gastric cancer (GC) remains poorly understood. Here, we show that SATB1 plays critical role in GC progression. SATB1 upregulates in GC patients’ samples and shows co-apmlification with a subset of oncogenic proteins (PRICKLE2, ZEB1, CBWX7, WWTR1, ENAH, DZIP1, IGSF11, ZSCAN18, GFRA2, GFRA1, FGFR1, HDAC4, GHR, TIMP3, CLIP4, TAGLN and ILK) in different subtypes of GC. SATB1 shows positive correlation with GC promoting oncogenes and enhances the expression of metastasis associated genes in GC samples to potentiate GC progression. SATB1 enhances WNT/NOTCH signaling axis in GC samples. In contrast, STAB1 suppresses a network of tumor suppressor genes in GC samples. Moreover, SATB1 expression negatively correlates with GC patient’s survival. Importantly, we found that SATB1 co-amplified genes CLIP4, DZIP1 and PRICKLE2 independently involve in GC progression. Overexpression of CLIP4, DZIP1 and PRICKLE2 show poor survival rates in GC patients. DZIP1 empowers AKT3/FGF2/FGFR1 and CXCR3/CXCR6 in GC patients. PRICKLE2 enhances GC progression by targeting FGFR1/NOTCH3/WNT4 signaling. Taken together, these results identified novel roles of SATB1, CLIP4, DZIP1 and PRICKLE2 in the GC invasion, migration and metastasis using cancer bioinformatics approach. These results highlights clinical significance of SATB1, CLIP4, DZIP1 and PRICKLE2 in GC patients and furthermore, these proteins may serve as prognostic markers in GC. These results also provide SATB1, CLIP4, DZIP1 and PRICKLE2 as potential chemotherapeutic targets in treatment of gastric cancer patients.