scholarly journals Abnormal N-glycosylated CPXM1 promotes gastric cancer metastasis through ITGB2 / FAK pathway

2021 ◽  
Author(s):  
Jun Du ◽  
Mengxiang Zhu ◽  
Wenwu Yan ◽  
Jin Guo Wang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Bioinformatics Analysis ◽  
Abdominal Cavity ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Malignant Phenotype ◽  
Gastric Cancer Cells ◽  
Glycosylation Sites

Abstract Background: To explore the molecular mechanism of CPXM1 in gastric cancer (GC) metastasis.Methods: Based on the difference in expression of CPXM1 mRNA in GC tissues and normal gastric mucosa tissues in public databases, rt-PCR, WB and IHC staining experiments were performed to verify the expression of CPXM1 in fresh GC tissues. Bioinformatics analysis predicts the possible signal pathways of co-expression genes in CPXM1 overexpression group. The malignant phenotypes of GC cells was verified by in vivo and in vitro experiments. Using tunicamycin to inhibit the N-glycosylation of CPXM1 and constructing mutations. The plasmid further validated the specific N-glycosylation sites that affect the malignant phenotype of gastric cancer cells.Results: CPXM1 mRNA expression was significantly increased in GC tissues. The results of IHC staining and WB indicated that there was no difference in the expression of CPXM1 at the protein level. Knocking down CPXM1 expression in HGC-27 cells can significantly inhibit its migration and invasion ability. Increasing the expression of CPXM1 in MGC-803 and BGC-823 cell lines can significantly promote its migration and invasion capabilities. CPXM1 can also promote the adhesion of GC cells and change the cytoskeleton structure. The results of in-vivo experiments show that CPXM1 can promote the metastasis of GC cells in the abdominal cavity of nude mice. Bioinformatics analysis showed that the co-expressed genes of the CPXM1 high expression group were mainly enriched in cell adhesion function, and the experimental results verified that CPXM1 may promote the adhesion and metastasis of gastric cancer cells through the ITGB2/FAK signaling pathway. Through N-glycosylation site prediction and WB results, it was found that CPXM1 had abnormal N-glycosylation in GC tissues. Tunicamycin can reverse the ability of CPXM1 that promote the invasion of GC cells. After respectively mutating the N-glycosylation sites on CPXM1, it was found that N210 site is the key site for CPXM1 to promote the adhesion and invasion of GC cells.Conclusion: CPXM1 is upgraded in GC. CPXM1 can promote the adhesion, migration and invasion of GC cells and change cytoskeleton structure. The N210 site on CPXM1 is a key site affecting the malignant phenotype of GC.

Downregulation of CCKBR Expression Inhibits the Proliferation of Gastric Cancer Cells, Revealing a Potential Target for Immunotoxin Therapy

2022 ◽  
Vol 22 ◽  
Author(s):  
Meng Li ◽  
Jiang Chang ◽  
Honglin Ren ◽  
Defeng Song ◽  
Jian Guo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Aberrant Expression ◽  
Promising Target ◽  
The Impact

Background Increased CCKBR expression density or frequency has been reported in many neoplasms. Objective We aimed to investigate whether CCKBR drives the growth of gastric cancer (GC) and its potential as a therapeutic target of immunotoxins. Methods A lentiviral interference system was used to generate CCKBR-knockdown gastric cancer cells. Cell Counting Kit-8 and clonogenic assays were used to evaluate cell proliferation. Wound-healing and cell invasion assays were performed to evaluate cell mobility. Cell cycle was analyzed by flow cytometry. Tumor growth in vivo was investigated using a heterologous tumor transplantation model in nude mice. In addition, we generated the immunotoxin FQ17P and evaluated the combining capacity and tumor cytotoxicity of FQ17P in vitro. Results Stable downregulation of CCKBR expression resulted in reduced proliferation, migration and invasion of BGC-823 and SGC-7901 cells. The impact of CCKBR on gastric cancer cells was further verified through CCKBR overexpression studies. Downregulation of CCKBR expression also inhibited the growth of gastric tumors in vivo. Furthermore, FQ17P killed CCKBR-overexpressing GC cells by specifically binding to CCKBR on the tumor cell surface. Conclusion The CCKBR protein drives the growth, migration, and invasion of gastric cancer cells, and it might be a promising target for immunotoxin therapy based on its aberrant expression, functional binding interactions with gastrin, and subsequent internalization.

scholarly journals MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yixun Lu ◽  
Benlong Zhang ◽  
Baohua Wang ◽  
Di Wu ◽  
Chuang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cancer Tissues ◽  
Gastric Cancer Progression

Abstract Background Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. Methods Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. Results GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. Conclusions MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.

scholarly journals The Roles of Beclin 1 Expression in Gastric Cancer: A Marker for Carcinogenesis, Aggressive Behaviors and Favorable Prognosis, and a Target of Gene Therapy

2020 ◽  
Vol 10 ◽  
Author(s):  
Hua-chuan Zheng ◽  
Shuang Zhao ◽  
Hang Xue ◽  
En-hong Zhao ◽  
Hua-mao Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gene Therapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Gastric Carcinogenesis ◽  
Beclin 1 ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Gastric Cancer Cells ◽  
Potential Marker

Beclin 1 is encoded by Becn1, and plays a role in tumorigenesis, neurodegeneration, apoptosis and autophagy. Here, the aggressive phenotypes and relevant proteins were examined after Beclin 1 expression was altered in gastric cancer cells. We also observed the effects of Beclin 1 on gastric carcinogenesis using Becn1 knockout mice. Finally, clinicopathological significances of Beclin 1 expression were analyzed using meta- and bioinformatics analyses. Becn1 overexpression was found to inhibit proliferation, glucose metabolism, migration and invasion of gastric cancer cells, whereas its knockdown caused the opposite effects. Beclin 1 suppressed the tumor growth by decreasing proliferation and increasing apoptosis. The heterozygous abrogation of Becn1 in gastric pit, parietal and chief cells could not cause any epithelial lesion. Beclin 1-mediated chemoresistance was closely linked to the autophagy, Bax underexpression, and the overexpression of Bcl-2, LRP1, MDR1, and ING5. Bioinformatics analysis showed higher Becn1 mRNA expression in intestinal- than diffuse-type carcinomas (P<0.05), and in male than female gastric cancer patients (P<0.05). Becn1 hyperexpression was positively associated with both overall and progression-free survival rates of the cancer patients (P<0.05). Meta-analysis showed that down-regulated Beclin 1 expression in gastric cancer was positively with lymph node metastasis, TNM staging, dedifferentiation and poor prognosis (P<0.05). Becn1-related signal pathways in gastric cancer included prostate, lung, renal, colorectal, endometrial and thyroid cancers, glioma, and leukemia, the metabolism of amino acid, lipid and sugar, and some signal pathways of insulin, MAPK, TRL, VEGF, JAK-STAT, chemokine, p53, lysosome, peroxidome and ubiquitin-mediated protein degradation (P<0.05). These suggested that Beclin 1 might be considered as a potential marker of gastric carcinogenesis, aggressiveness and prognostic prediction, and as a target of gene therapy in gastric cancer.

scholarly journals Yiqi Huayu Jiedu Decoction Inhibits the Invasion and Metastasis of Gastric Cancer Cells through TGF-β/Smad Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ting-Ting Wu ◽  
Jun Lu ◽  
Pei-Qiu Zheng ◽  
Shen-Lin Liu ◽  
Jian Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells ◽  
Smad Pathway ◽  
Immunohistochemical Assay

Background.Yiqi Huayu Jiedu Decoction (YHJD) can obviously improve the quality of life of those patients with gastric cancer and prolong their survival.Methods. In vitro experiments, we observe YHJD’s effect on the cells’ proliferation by MTT assay. Cell adhesion assay, wound-healing assay, and Transwell invasion assay serve to detect its influence on cells’ adhesion, migration, and invasion, respectively. Inhibitor (10 μM/L of SB431542) and activator (10 ng/mL of TGF-β) of TGF-β/Smad pathway were used to estimate whether YHJD’s impact on the biological behavior of gastric cancer cells was related to TGF-β/Smad pathway. In in vivo studies, YHJD was administered to the nude mice transplanted with gastric cancer to observe its effect on the tumor. Western blotting and immunohistochemical assay were used to test relevant cytokines of TGF-β/Smad pathway and epithelial-mesenchymal transition (EMT) in MGC-803 cells and the tumor bearing nude mice.Results.YHJD inhibited proliferation, adhesion, migration, and invasion of MGC-803 gastric cancer cells in vitro. In in vivo studies, YHJD reduced the volume of the transplanted tumors. It also enhanced the expression of E-cadherin and decreased the levels of N-cadherin, TGF-β, Snail, and Slug in both MGC-803 cells and the transplanted tumor by western blot assay. The immunohistochemical assay revealed that YHJD raised E-cadherin in the tumors of the mice; on the contrary, the expression of N-cadherin, Twist, vimentin, TGF-βR I, p-Smad2, p-Smad3, Snail, and Slug reduced.Conclusion. YHJD can effectively inhibit the invasion and metastasis of gastric cancer cells. The mechanism may be related to TGF-β/Smad pathway.

scholarly journals Efficacy of a Hypotonic Treatment for Peritoneal Dissemination from Gastric Cancer Cells: AnIn VivoEvaluation

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Atsushi Shiozaki ◽  
Daisuke Ichikawa ◽  
Kenichi Takemoto ◽  
Yoshito Nako ◽  
Shingo Nakashima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Nude Mice ◽  
Peritoneal Dissemination ◽  
Abdominal Cavity ◽  
Gastric Cancer Cells ◽  
Abdominal Organs ◽  
Hypotonic Treatment

The aim of the present study was to determine the efficacy of a hypotonic treatment for peritoneal dissemination from gastric cancer cells using anin vivomodel. We firstly evaluated the toxicity of a peritoneal injection of distilled water (DW) (2 mL for 3 days) in mice. Macroscopic and microscopic examinations revealed that the peritoneal injection of DW did not severely damage the abdominal organs of these mice. MKN45 gastric cancer cells preincubated with NaCl buffer or DW for 20 minutesin vitrowere then intraperitoneally injected into nude mice, and the development of dissemination nodules was analyzed. The total number, weight, and volume of the dissemination nodules were significantly decreased by the DW preincubation. We then determined whether the peritoneal injection of DW inhibited the establishment of peritoneal dissemination. After a peritoneal injection of MKN45 cells into nude mice, NaCl buffer or DW was injected into the abdominal cavity for 3 days. The total volume of dissemination nodules was significantly lower in DW-injected mice than in NaCl-injected mice. In conclusion, we demonstrated the safeness of a peritoneal injection of DW. Furthermore, the development of dissemination nodules from gastric cancer cells was prevented by a preincubation with or peritoneal injection of DW.

scholarly journals LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target

Oncogene ◽  
2021 ◽  
Author(s):  
Xi Kang ◽  
Weilin Li ◽  
Weixin Liu ◽  
Han Liang ◽  
Jingyu Deng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Peritoneal Metastasis ◽  
Therapeutic Target ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion

AbstractPeritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.

LINC01207 is up-regulated in gastric cancer tissues and promotes disease progression by regulating miR-671-5p/DDX5 axis

2021 ◽  
Author(s):  
Hongquan Liu ◽  
Xiaoyu Liu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Bioinformatics Analysis ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Downstream Target ◽  
Proliferation And Metastasis ◽  
Cancer Tissues

Abstract LINC01207 is involved in the progression of some cancers. This study was designed to delve into the biological function and mechanism of LINC01207 in gastric cancer. qPCR was adopted to examine the expression levels of LINC01207, miR-671-5p, DDX5 mRNA in gastric cancer tissues and cells. After LINC01207 was overexpressed or depleted, MTT and BrdU assays were conducted to detect cell proliferation. Transwell assay was employed to detect cell migration and invasion. Western blot was used to detect the expression of DDX5 protein in cells. Bioinformatics analysis, luciferase reporter assay and RNA pull-down assay were performed to predict and validate the binding site between miR-671-5p and LINC01207 or DDX5. LINC01207, DDX5 mRNA were up-regulated in gastric cancer, while miR-671-5p was down-regulated; high expression of LINC01207 and transfection of miR-671-5p inhibitors facilitated the proliferation of gastric cancer cells; however, knocking down LINC01207 and the overexpression of miR-671-5p mimics had opposite biological effects. LINC01207 and miR-671-5p were interacted and miR-671-5p was negatively regulated by LINC01207. MiR-671-5p could reverse the function of LINC01207. DDX5 was a downstream target of miR-671-5p and was positively modulated by LINC01207. LINC01207 promotes the proliferation and metastasis of gastric cancer cells by regulating miR-671-5p/DDX5 axis.

scholarly journals Chrysin Induced Cell Apoptosis Through H19/let-7a/COPB2 Axis in Gastric Cancer Cells and Inhibited Tumor Growth

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Chen ◽  
Qirong Li ◽  
Ziping Jiang ◽  
Chengshun Li ◽  
Haobo Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Non Coding Rna ◽  
Differentially Expressed Mrna

BackgroundChrysin is a natural flavone that is present in honey and has exhibited anti-tumor properties. It has been widely studied as a therapeutic agent for the treatment of various types of cancers. The objectives of this present study were to elucidate how chrysin regulates non-coding RNA expression to exert anti-tumor effects in gastric cancer cells.MethodsThrough the use of RNA sequencing, we investigated the differential expression of mRNAs in gastric cancer cells treated with chrysin. Furthermore, COPB2, H19 and let-7a overexpression and knockdown were conducted. Other features, including cell growth, apoptosis, migration and invasion, were also analyzed. Knockout of the COPB2 gene was generated using the CRISPR/Cas9 system for tumor growth analysis in vivo.ResultsOur results identified COPB2 as a differentially expressed mRNA that is down-regulated following treatment with chrysin. Moreover, the results showed that chrysin can induce cellular apoptosis and inhibit cell migration and invasion. To further determine the underlying mechanism of COPB2 expression, we investigated the expression of the long non-coding RNA (lncRNA) H19 and microRNA let-7a. Our results showed that treatment with chrysin significantly increased let-7a expression and reduced the expression of H19 and COPB2. In addition, our results demonstrated that reduced expression of COPB2 markedly promotes cell apoptosis. Finally, in vivo data suggested that COPB2 expression is related to tumor growth.ConclusionsThis study suggests that chrysin exhibited anti-tumor effects through a H19/let-7a/COPB2 axis.

scholarly journals CircCNIH4 inhibits gastric cancer progression via regulating DKK2 and FRZB expression and Wnt/β-catenin pathway

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Qi Shi ◽  
Chuanwen Zhou ◽  
Rui Xie ◽  
Miaomiao Li ◽  
Peng Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Gastric Cancer Cells ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism. Methods The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of β-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer. Results CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/β-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo. Conclusion Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/β-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.

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

2022 ◽  
Author(s):  
Sheng-Mao Wu ◽  
Yee-Jee Jan ◽  
Shih-Chuan Tsai ◽  
Hung-Chuan Pan ◽  
Chin-Chang Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Peritoneal Dissemination ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Potential Therapeutic Target ◽  
Metastatic Dissemination ◽  
Over Expression

Abstract Background and purpose Histone 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 approach Clinical 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 results HDAC3 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 implications Honokiol acts by suppressing HDAC3-mediated EMT and metastatic signaling. By prohibiting HDAC3, metastatic dissemination of gastric cancer may be blocked. Graphical abstract Conceptual 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.

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