Inhibition of Nuclear Factor-κB Enhances the Antitumor Effect of Paclitaxel Against Gastric Cancer with Peritoneal Dissemination in Mice

Background

Intraperitoneal (i.p.) administration of paclitaxel is useful for treating malignant tumors with peritoneal dissemination, but the therapeutic efficacy is limited. Chemoresistance due to paclitaxel-induced nuclear factor-kappa B (NF-κB) activation is an important cause of suboptimal therapeutic efficacy.

Aims

The purpose of this study was to prove that addition of nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor and an NF-κB inhibitor, to i.p. paclitaxel enhances antitumor effects of paclitaxel against gastric cancer with peritoneal dissemination.

Methods

In vitro, we assessed NF-κB activity and apoptosis in response to treatment with FUT-175 alone, paclitaxel alone, or a combination of FUT-175 and paclitaxel in a human gastric cancer cell line (MKN-45). In vivo, we established peritoneal dissemination in nude mice by i.p. injection of MKN-45 cells. The animals received i.p. injections of FUT-175 alone three times a week (FUT-175 group), of paclitaxel alone once a week (paclitaxel group), or a combination of FUT-175 and paclitaxel (combination group) three times and once a week, respectively.

Results

In the combination group, paclitaxel-induced NF-κB activation was inhibited and apoptosis was enhanced in comparison with those in the other groups both in vitro and in vivo. In the combination group, number and weight of peritoneal nodules were significantly lower than those in the paclitaxel group (p = 0.0009 and p = 0.0417, respectively). In the survival analysis, the combination group had a significantly better survival than the paclitaxel group (p = 0.0048).

Conclusion

FUT-175 enhances the antitumor effect of i.p. paclitaxel against gastric cancer with peritoneal dissemination by inhibiting NF-κB activation in mice.     

Nuclear factor-κB activation by type II collagen peptide in articular chondrocytes: its inhibition by hyaluronan via the receptors

Objective

This study aimed to examine nuclear factor-κB (NF-κB) activation by a synthetic peptide from type II collagen fragment (CB12-II) and its inhibition by hyaluronan (HA) via its receptors, CD44, and intercellular adhesion molecule-1 (ICAM-1) in chondrocytes.

Methods

Osteoarthritic cartilage explants or chondrocytes in monolayer were cultured with CB12-II. Secreted levels of matrix metalloproteinase (MMP)-13 in conditioned media and NF-κB activation in chondrocytes were determined by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Cultures were pretreated with HA to evaluate the inhibitory effect on CB12-II action, and the role of HA receptors in HA effect was investigated using antibodies to CD44 and ICAM-1.

Results

CB12-II stimulated phosphorylation and nuclear translocation of NF-κB, leading to increased MMP-13 production. HA suppressed NF-κB activation and MMP-13 induction by CB12-II. The individual antibody to CD44 or ICAM-1 partially reversed HA effect on CB12-II action, and both antibodies in combination completely blocked the HA effect.

Conclusions

This study clearly demonstrates that CB12-II activates NF-κB for MMP-13 induction and that HA inhibits CB12-II action through interaction with CD44 and ICAM-1 in chondrocytes. HA administration into osteoarthritic joints could suppress the catabolic action of matrix degradation products such as CB12-II as a potent NF-κB inhibitor.     

Guggulsterone enhances antitumor activity of gemcitabine in gallbladder cancer cells through suppression of NF-κB

Purpose

Patients with gallbladder cancer usually have a poor prognosis, and effective standard chemotherapeutic regimens have not been established. The anticancer activities of guggulsterone have been demonstrated in various cancer cells. The aims of the study were to determine the effect of guggulsterone on gallbladder cancer cells and to investigate whether treatment with guggulsterone influences the antitumor activities of gemcitabine.

Methods

The Dojindo Cell Counting Kit-8 assay was used to determine the inhibition of proliferation by drugs in TGBC1 and TGBC2 cells. Cell migration and invasion were examined using 24-well inserts and Matrigel?-coated invasion chambers. The activities of NF-κB p65, VEGF-C, and MMP-2 were measured by ELISA.

Results

Guggulsterone inhibited the proliferation and suppressed migration and invasion of gallbladder cancer cells in a dose-dependent manner. Guggulsterone significantly decreased NF-κB p65, VEGF-C, and MMP-2 activities in the gallbladder cancer cells examined. Gallbladder cancer cells treated with a combination of guggulsterone and gemcitabine demonstrated significant inhibition of cell proliferation and invasion when compared to treatment with gemcitabine alone. In addition, NF-κB p65 activation decreased significantly in cells treated with a combination of guggulsterone and gemcitabine when compared to treatment with gemcitabine alone.

Conclusions

Guggulsterone exhibits anticancer activities and enhances the antitumor activities of gemcitabine through the suppression of NF-κB activation in gallbladder cancer cells. These results suggest that guggulsterone could be a potential therapeutic option for patients with gallbladder cancer.     

HOXA10 Promotes Cell Invasion and MMP-3 Expression Via TGFβ2-Mediated Activation of the p38 MAPK Pathway in Pancreatic Cancer Cells

Background

HOXA10 is closely related to tumor progression in many human cancers. However, the role of HOXA10 in pancreatic cancer remains unclear. The aim of this study was to determine the involvement of HOXA10 in pancreatic cancer cell invasion and migration.

Methods

The effect of HOXA10 on the invasion and migration of pancreatic cancer cells was assessed by invasion and migration assays. The protein of transforming growth factor beta-2 (TGFβ2) was neutralized by TGFβ2 blocking antibody. The activation of p38 was inhibited by SB239063.

Results

HOXA10 could promote the invasion and migration of pancreatic cancer cells. Knockdown of HOXA10 decreased the expressions of TGFβ2 and matrix metallopeptidase-3 (MMP-3) and suppressed the activation of p38. Conversely, overexpression of HOXA10 increased the levels of TGFβ2 and MMP-3. Further experiments identified that TGFβ2 contributed to the HOXA10-promoted invasion and migration and regulated MMP-3 expression and p38 activation. Additionally, inhibition of p38 suppressed cell invasion and MMP-3 expression in pancreatic cancer cells.

Conclusions

HOXA10 promotes cell invasion and MMP-3 expression of pancreatic cancer cells via TGFβ2-p38 MAPK pathway. Thus, HOXA10 could be a useful target for the treatment of pancreatic cancer.     

Notch信号通路对人胰腺癌细胞NF—κB活性和侵袭能力的影响

背景：Notch信号通路在多种人类恶性肿瘤的发生、发展中起关键作用。研究显示Notch与NF—κB信号通路之间的交互作用可促进胰腺癌进展。目的：明确Notch信号通路对胰腺癌侵袭性的影响及其可能机制。方法：体外培养人胰腺癌细胞株BxPC3,以Notch-1siRNA下调其Notch-1表达,同时设置转染对照siRNA的阴性对照组和不予siRNA干扰的空白对照组。以Transwell细胞侵袭实验观察各组BxPC3细胞的侵袭能力,电泳迁移率变动分析（EMSA）检测NF—κB活性,蛋白质印迹法检测Notch-1、NF—KBp65、血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP．9）蛋白表达。结果：经Notch-1siRNA干扰、Notch-1表达下调的BxPC3细胞,Transwell细胞侵袭实验穿膜细胞数较空白对照组和阴性对照组显著减少（26．5±1．3对78．5±2．4和76．7±2．2,P〈0．01）,NF—κB活性显著降低（P〈0．01）,NF-κB p65、VEGF、MMP-9蛋白表达显著下调（P〈0．05）。结论：Notch-1可通过激活NF—κB促进其下游基因VEGF、MMP-9表达,由此增强胰腺癌的侵袭性。     

Insulin-Like Growth Factor 1 Receptor Promotes the Growth and Chemoresistance of Pancreatic Cancer

Background

Insulin-like growth factor 1 receptor (IGF1R) plays important roles in the progression of pancreatic cancer. However, the underlying mechanism remains unclear.

Aims

The purpose of this study was to investigate the effects of IGF1R knockdown on the proliferation, apoptosis and chemosensitivity of pancreatic cancer cells, and explore the possible mechanisms.

Methods

Pancreatic cancer cells expressing IGF1R shRNA were established, and the cell proliferation, colony formation, and chemosensitivity to gemcitabine were examined in vitro. The activation of AKT and NF-κB was detected by Western blot analysis and luciferase assay, respectively. Xenograft mice models were established to evaluate the in vivo anti-tumor effects of IGF1R knockdown.

Results

IGF1R knockdown notably inhibited pancreatic cancer cell proliferation and colony formation, induced apoptosis, and inhibited xenograft tumor growth. Moreover, IGF1R knockdown significantly enhanced chemosensitivity to gemcitabine in pancreatic cancer cells, and this was correlated with the inhibition of PI3K/AKT and NF-κB pathways.

Conclusions

IGF1R knockdown suppresses tumor growth and enhances chemosensitivity in pancreatic cancer via the inhibition of PI3K/AKT and NF-κB pathways, and is a promising approach to overcome the chemoresistance of pancreatic cancer.     

Protease-activated receptor-2 regulates cyclooxygenase-2 expression in human bile duct cancer via the pathways of mitogen-activated protein kinases and nuclear factor kappa B

Background/purpose

Recent studies have suggested that protease-activated receptor-2 (PAR-2) activity correlates with cell proliferation and tumor growth, and its activation induces expression of cyclooxygenase-2 (COX-2). However, no previous reports have investigated PAR-2 signaling pathways in bile duct cancer. The aim of this study was to determine whether PAR-2 activation can regulate COX-2 expression via mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-??B) in human bile duct cancer cells.

Methods

We immunohistochemically examined PAR-2 and COX-2 expression in 104 resected human specimens of extrahepatic bile duct cancer. We then determined how inhibitors of MAPKs and NF-??B signaling pathways influence COX-2 expression under PAR-2 activation in HuCCT1 and TKKK, human bile duct cancer cell lines.

Results

PAR-2 and COX-2 proteins were immunohistochemically recognized in 63 and 57% of specimens and were significantly correlated. PAR-2 agonist peptide activated mRNA and protein expression of COX-2 in HuCCT1 and TKKK. Pharmacologic blockade of p44/42 or p38 MAPK significantly inhibited PAR-2-activated mRNA and protein expression of COX-2 in both cells. COX-2 protein expression was also inhibited by the blocker of NF-??B pathway in both cells.

Conclusions

PAR-2 may regulate COX-2 expression in human bile duct cancer via the MAPKs and NF-??B pathways.     

Repetitive hypoglycaemia increases serum adrenaline and induces monocyte adhesion to the endothelium in rat thoracic aorta

Aims/hypothesis

Severe hypoglycaemia associated with diabetes management is a potential risk for cardiovascular diseases. However, the effect and mechanism of hypoglycaemia on the progression of atherosclerosis remains largely unknown. As a first step towards elucidating the above, we investigated the effect of hypoglycaemia on monocyte?Cendothelial interaction.

Methods

Insulin was injected intraperitoneally once every 3?days for 5?weeks in Goto?CKakizaki rats, a non-obese rat model of type 2 diabetes. We counted the number of monocytes adherent to the endothelium of thoracic aorta as an index of early atherosclerogenesis. Cultured HUVEC were used to investigate the mechanism of action.

Results

Insulin treatment increased the number of monocytes adherent to the vascular endothelium. This increase was abrogated by injection of glucose with insulin. Amosulalol, an ??-1 and ??-adrenoreceptor antagonist, suppressed monocyte adhesion to endothelium and levels of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in the endothelial surface, which had been enhanced by insulin-induced hypoglycaemia. In HUVEC, adrenaline (epinephrine) significantly increased nuclear translocation of nuclear factor-??B (NF-??B) p65 and levels of adhesion molecules, effects that were abrogated following addition of SQ22536, a specific adenyl cyclase inhibitor.

Conclusions/interpretation

Our data indicate that repetitive hypoglycaemia induced by insulin enhanced monocyte adhesion to endothelial cells in Goto?CKakizaki rat aorta through enhanced adrenaline activity and that the latter stimulated intracellular cAMP, leading to nuclear translocation of NF-??B with subsequent production of adhesion molecules in endothelial cells.     

Carbon Monoxide Liberated from Carbon Monoxide-Releasing Molecule Exerts an Anti-inflammatory Effect on Dextran Sulfate Sodium-Induced Colitis in Mice

Background

Endogenous carbon monoxide (CO) is one of the three products of heme degradation by heme oxygenase-1 (HO-1) and exerts novel anti-inflammatory and anti-apoptotic effects as a gaseous second messenger. The purpose of this investigation was to determine whether exogenous CO could modulate intestinal inflammation.

Methods

Acute colitis was induced with 2% DSS in male C57BL/6 mice. CO-releasing molecule-2 (CORM-2; tricarbonyldichlororuthenium(II) dimer) was intraperitoneally administered twice daily and the disease activity index (DAI) was determined. We measured tissue-associated myeloperoxidase (MPO) activity as an index of neutrophil infiltration, and the production of keratinocyte chemoattractant (KC) and tumor necrosis factor-?? (TNF-??) protein in the intestinal mucosa. In an in-vitro study, young adult mouse colonic epithelial (YAMC) cells were incubated with TNF-??, and KC mRNA/protein expression and nuclear translocation of nuclear factor-kappa B (NF-??B) were measured with or without CORM-2 treatment.

Results

After DSS administration, DAI score increased in a time-dependent manner, and this increase was ameliorated by CORM-2 treatment. Increases in MPO activity and in the production of KC and TNF-?? after DSS administration were significantly inhibited by CORM-2. TNF-??-induced KC production in YAMC cells was also inhibited by CORM-2 treatment. Further, nuclear translocation of NF-??B in YAMC cells was inhibited by CORM-2.

Conclusion

CORM-liberated CO significantly inhibited inflammatory response in murine colitis by inhibition of cytokine production in the colonic epithelium. These results suggest that CO could become a new therapeutic molecule for inflammatory bowel disease.     

Triptolide triggers the apoptosis of pancreatic cancer cells via the downregulation of Decoy receptor 3 expression

Purpose

Triptolide (TPL) is a diterpenoid triepoxide that effectively induces apoptosis in a wide variety of cancer cells. However, the detailed mechanism by which TPL activates caspase cascade remains elusive. This study aimed to examine the antitumor effects of TPL against pancreatic cancer and investigate the underlying mechanism.

Methods

Cell proliferation was evaluated by sulforhodamine B assay. The apoptosis was evaluated by caspase activity assay, Western blot and flow cytometry. DcR3 level was measured by ELISA. AsPC-1 xenografts were established to compare the in vivo antitumor effects of TPL and Gemcitabine.

Results

TPL inhibited the proliferation and induced the apoptosis of pancreatic cancer cells in a dose- and time-dependent manner. TPL also inhibited DcR3 expression in a dose- and time-dependent manner. siRNA-mediated DcR3 knockdown sensitized pancreatic cancer cells to TPL-induced apoptosis. In vivo, DcR3 siRNA significantly enhanced TPL-induced apoptosis and tumor growth inhibition. Moreover, TPL showed less toxicity compared to Gemcitabine in mice model.

Conclusions

TPL induces the apoptosis of pancreatic cancer cells via the downregulation of DcR3 expression and has the potential as an effective agent against pancreatic cancer.     

Analysis of the contribution of nasopharyngeal epithelial cancer cells to the induction of a local inflammatory response

Purpose

We investigated the local contribution of nasopharyngeal epithelial cancer cells to the inflammatory process.

Materials and methods

THP-1 monocytes were treated with phorbol 12-myristate 13-acetate to induce the production of differentiated macrophages (D-THP-1), which were subsequently activated by lipopolysaccharide (LPS) (10?ng/ml). The production of pro-inflammatory cytokines in D-THP-1 cells was detected by ELISA and qRT-PCR. The effects of conditioned media harvested from LPS-treated D-THP-1 cells were investigated with regard to cell proliferation (MTT), production of pro-inflammatory cytokines (ELISA) and activation of NF-??B and STAT3 (western blot) in the nasopharyngeal epithelial cancer cell line 5?C8F.

Results

LPS induced the production of the pro-inflammatory cytokines TNF-?? (875.1?±?68.31?pg/ml), IL-6 (42.2?±?5.32?pg/ml), IL-1?? (9.6?±?1.34?pg/ml) and IL-8 (19.3?±?3.47?pg/ml) in D-THP-1 cells significantly (P?P?P?P?Conclusions Nasopharyngeal epithelial cancer cells may play a significant role in maintaining and amplifying the inflammation process via activation of NF-??B and STAT3 pathway and through the local production of pro-inflammatory cytokines, which recruit and activate additional immune cells in the nasopharyngeal path and promote tumour progression.     

The Expression of Both Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 in Tissues Is Associated with Poor Prognosis in Colorectal Cancer Patients

Background

The role of peroxisome proliferator-activated receptor delta (PPAR ??) in the development and progression of colorectal cancer (CRC) remains controversial.

Aims

We investigated the impact of PPAR ?? expression in tissues on liver metastasis of CRC.

Methods

We analyzed samples of primary CRC and matched normal adjacent tissues from 52 patients for the expression of PPAR ??, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with clinical characteristics and prognosis of patients were studied.

Results

The number of patients positive for PPAR ??, COX-2, CXCR4, and VEGF-A was 25, 33, 18, and 19, respectively. Among the PPAR ?? (+)/COX-2 (+), PPAR ?? (?)/COX-2 (+), PPAR ?? (+)/COX-2 (?), and PPAR ?? (?)/COX-2 (?) patient groups, PPAR ?? (+)/COX-2 (+) patients had the highest incidence of liver metastasis (p < 0.01). PPAR ?? (+)/COX-2 (+) expression was a significant independent prognostic factor (HR = 7.108, 95% CI 1.231?C41.029, p = 0.0283) by Cox proportional analysis. PPAR ?? (+)/COX-2 (+) patients had the highest positivity for CXCR4 or VEGF-A in tissues (p < 0.01). Among the patients in the CXCR4 (+)/VEGF-A (+), CXCR4 (+)/VEGF-A (?), CXCR4 (?)/VEGF-A (+), and CXCR4 (?)/VEGF-A (?) groups, CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis (p < 0.01).

Conclusions

The expression of both PPAR ?? and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients.     

Stented pancreaticojejunostomy (with video)

Background/purpose

Using a standardized technique for pancreaticojejunostomy that we term ??pair-watch suturing technique??, we prospectively analyzed the effects of a pancreatic stent tube for preventing pancreatic fistula and furthermore evaluated which perioperative factors had an influence on the development of pancreatic fistula.

Operative procedure

Before anastomosis, we imagine the faces of a pair of wristwatches on the jejunal hole and pancreatic duct. The first stitch was put between 9?o??clock on the pancreatic side and 3?o??clock on the jejunal side, and a total of 7 stitches were put in the posterior wall, followed by 5 stitches in the anterior wall. Using this technique, twelve stitches can be sutured in the first layer anastomosis regardless of the caliber of the pancreatic duct.

Patients and methods

From March 2007 to April 2009, 55 consecutive patients who underwent the pair-watch suturing technique were divided into two groups: stent (n?=?28) and no-stent (n?=?27). The incidence rate of pancreatic fistula was statistically analyzed. From March 2007 to March 2011, 102 consecutive patients were retrospectively divided into two groups according to the International Study Group on Pancreatic Fistula criteria: postoperative pancreatic fistula (POPF) and non-POPF.

Results

Perioperative factors were almost the same between the stent and no-stent groups, and the incidence of pancreatic fistula was very similar: 10.7% in the stent group and 14.8% in the no-stent group. Additionally, all patients who developed pancreatic fistula belonged to grade A. Among 102 patients, 15 (14.7%) were identified as having pancreatic fistula: 9 (8.8%) in grade A, 5 (4.9%) in grade B, and 1 (0.9%) in grade C. Comparing the POPF and non-POPF groups, we could not detect any significant risk factors for the development of pancreatic fistula.

Conclusion

We consider that the pair-watch suturing technique is less susceptible to any factors, providing reliable anastomosis for any size of pancreatic duct and any texture of remnant pancreas.     

NF-κB基因对胰腺癌细胞侵袭作用的影响及机制

目的探讨NF-κB基因对胰腺癌细胞侵袭的影响及机制。方法应用NF-κB基因小于扰RNA（siRNA）转染处理人胰腺癌PANC-1细胞,采用Westernblot方法检测NF-KB蛋白水平,采用Boyden小室模型试验检测癌细胞侵袭能力。收集转染48h的癌细胞,采用包含有96个转移相关基因的芯片检测基因表达情况;根据基因芯片结果,随机抽取3个表达明湿变化的基因采用荧光实时定量PCR（RT—PCR）验证基因芯片结果。结果转染组癌细胞NF-κB蛋白水平下调（P〈0．05）,且与时间和浓度相关。与对照组比较,转染组细胞的穿膜细胞数减少（P〈0．05）,且呈浓度依赖关系。基因芯片检测发现,96个基因中有11个基因表达出现明显变化,其中9个基因明显下调,包括基质金属蛋白酶2（MMP-2）、MMP-7和血管内皮生长因子（VEGF）,有2个基因出现明显上调。采用荧光RT—PCR方法检测MMP-2、MMP-7、VEGF基因表达,结果也发现这3个基因表达下调,且下调幅度与基因芯片结果一致。结论NF-κB基因siRNA转染可明昆抑制胰腺癌细胞的锚着不依赖性增殖和恶性侵袭,其机制可能与下调MMP-2、MMP-7和VEGF有关。     

Celecoxib suppresses proliferation and metastasis of pancreatic cancer cells by down-regulating STAT3 / NF-kB and L1CAM activities

Objective

To explore the molecular mechanisms of celecoxib-induced pancreatic cancer suppression in vivo and in vitro.

Matrix Metalloproteinase-14 Is a Negative Prognostic Marker for Patients with Gastric Cancer

Background

Matrix metalloproteinase-14 (MMP-14) has been considered to play an important role in invasion and metastasis of human solid tumor.

Aim

The present study aimed to investigate the association of MMP-14 with overall survival in human gastric cancer.

Methods

Gastric cancer and adjacent normal specimens were collected from 205 patients who had not received neoadjuvant chemotherapy. MMP-14 expression was investigated by immunohistochemistry assay and staining evaluation results were analyzed statistically in relation to overall survival of patients.

Results

MMP-14 expression proved to be increased in gastric cancer compared with that in normal tissues. It was also proved that MMP-14 expression was associated with tumor invasion, metastasis, and TNM stage while no correlations were detected between MMP-14 expression and age, sex, differentiation status, or Lauren’s classification. Moreover, patients with gastric cancer of MMP-14-positive expression tend to have worse overall survival compared with those with MMP-14 negative expression.

Conclusions

The present study confirmed the over-expression of MMP-14 in human gastric cancer and its association with tumor progression. It also provided the first evidence that MMP-14 expression in gastric cancer was an independent negative prognostic factor of patients.     

Receptor for activated C kinase 1 (RACK1): a regulator for migration and invasion in oral squamous cell carcinoma cells

Purpose

Receptor of activated protein kinase C 1 (RACK1) has been identified as an anchoring or adaptor protein in multiple intracellular signal transduction pathways. Our previous study has showed that the expression of RACK1 was paralleled with proliferation and correlated with metastasis and clinical outcome. However, the underlined mechanism has not been uncovered.

Materials and methods

We first selected a most effective siRNA among three siRNAs (siRNA-1, siRNA-2 and siRNA-3) targeting different regions in the RACK1 mRNA and re-evaluated the anticancer effect of RACK1 silencing on HSC-3 and Cal-27 cell lines by cell growth inhibition. And then, we investigated whether knockdown of RACK1 could inhibit cell adhesion, migration and invasion in these two cell lines. To further understand the molecular mechanism of RACK1 in these processes, the expressions of EGFR, pEGFR, HER2, MMP-2 and MMP-9 were detected by western blot.

Results

We verified that the silence of RACK1 gene in two OSCC cell lines could not only inhibit cell proliferation but also decrease the invasion, migration and adhesion capability of the tumor cells. Further, western blot analysis deduced that it might be related to the decrease in protein expression of EGFR, pEGFR, HER2, MMP-2 and MMP-9.

Conclusion

Our results clearly showed the significance of RACK1-induced OSCC cell migration, invasion and adhesion, which could explain the underlined mechanism of the effect of the gene on metastasis and clinical outcome. Also, our results confirmed its role to be a prognostic indicator and a promising drug target for OSCC cell metastasis.