6591

SNAI2

snail family zinc finger 2;SNAI2;snail family zinc finger 2

neural crest transcription factor SLUG|protein snail homolog 2|slug (chicken homolog), zinc finger protein|snail homolog 2|zinc finger protein SNAI2

8q11

protein-coding

In a previous study, we have identified Slug as selectively overexpressed in the highly invasive bladder cancer cells. Furthermore, Slug overexpression was correlated with metastasis in bladder cancer tissues. Here, we investigated the role and underlying mechanism of Slug in the process of growth, invasion and metastasis formation, and vascular leakage in a bladder cancer cell line T24. We knocked down in a bladder cancer cell line T24 by Slug siRNA, and the effects on invasion, metastasis, and proliferation were evaluated in vitro. A pseudometastatic model of bladder cancer in severe combined immunodeficient mice was used to assess the effects of Slug silencing on metastasis and angiogenesis development. Slug-specific siRNA in T24 cells led to a significant decrease in invasiveness and metastasis, proliferation rates, and angiogenesis in vitro. Slug-specific siRNA induced strong changes in cell invasiveness mainly through a mechanism of up-regulation of epithelial markers E-cadherin expression. Interestingly, E-cadherin-specific siRNA attenuated Slug siRNA-induced Matrigel invasion. Moreover, Slug-specific siRNA induced strong changes in microvessel counts in angiogenesis mainly through decreased activity of MMP-2, but not through cadherin expression and decreased activity of MMP-9. Restoration of MMP-2 expression in the Slug-silenced T24 cells resulted in an increased cell angiogenesis. Moreover, Slug-specific siRNA significantly reduced tumor growth by approximately 60% and inhibited metastasis and angiogenesis in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and a decreased expression of MMP-2 in tumor tissues. These data suggest that Slug regulates tumor growth, invasion and metastasis, and angiogenesis through E-cadherrin and MMPS passway. Blocking Slug signaling in bladder cancer may represent a novel strategy in the future to reduce metastatic disease burden in bladder cancer patients.

Androgen receptor (AR) has been indicated to be involved in bladder cancer progression. We showed androgen induced epithelial-mesenchymal transition (EMT) in AR-positive bladder cancer cells and promoted tumor metastasis in xenograft models. We subsequently identified that Slug was the mediator of EMT induced by androgen. Furthermore, upregulation of Slug was due to activation of Wnt/beta-catenin signaling in response to androgen. Finally, expression of AR showed strong correlation with loss of E-cadherin, higher expression of Slug and nuclear accumulation of beta-catenin in bladder tumor tissues. Taken together, our results suggest AR signaling promotes bladder cancer metastasis through Slug mediated EMT.

Regulatory networks orchestrated by key transcription factors (TFs) have been proposed to play a central role in the determination of stem cell states. However, the master transcriptional regulators of adult stem cells are poorly understood. We have identified two TFs, Slug and Sox9, that act cooperatively to determine the mammary stem cell (MaSC) state. Inhibition of either Slug or Sox9 blocks MaSC activity in primary mammary epithelial cells. Conversely, transient coexpression of exogenous Slug and Sox9 suffices to convert differentiated luminal cells into MaSCs with long-term mammary gland-reconstituting ability. Slug and Sox9 induce MaSCs by activating distinct autoregulatory gene expression programs. We also show that coexpression of Slug and Sox9 promotes the tumorigenic and metastasis-seeding abilities of human breast cancer cells and is associated with poor patient survival, providing direct evidence that human breast cancer stem cells are controlled by key regulators similar to those operating in normal murine MaSCs.

BACKGROUND: Among the different types of breast cancer, basal-like breast cancer (BLBC) has an extremely poor prognosis due to its high rate of recurrence and metastasis. The present study aimed to investigate the correlation between the expression of Slug, E-cadherin, and vimentin, and the clinicopathological characteristics and prognosis of patients with BLBC. We further inferred from these findings whether Slug leads to a poor prognosis in patients with BLBC through epithelial-mesenchymal transition (EMT). METHODS: Immunohistochemistry was performed for 441 patients with breast cancer to determine the expression levels of Slug, E-cadherin, and vimentin. The correlation between protein expression and clinicopathological characteristics of patients with BLBC was evaluated, and these patients were followed up to determine survival rate. RESULTS: High Slug and low E-cadherin expression in BLBC patients closely correlated with histological grade, lymph node metastasis, tumor-node-metastasis (TNM) stage, and lymphatic vessel metastasis. Survival analysis revealed that the poor prognosis of BLBC is associated with TNM stage, high Slug and vimentin expression, and low E-cadherin levels. CONCLUSIONS: High Slug expression is closely correlated with poor prognosis in patients with BLBC. We speculate that this may be attributed to the involvement of Slug in the EMT of BLBC.

The epithelial-mesenchymal transition (EMT) is a complex process that occurs during organogenesis and in cancer metastasis. Despite recent progress, the molecular pathways connecting the physiological and pathological functions of EMT need to be better defined. Here we show that the transcription factor Elf5, a key regulator of mammary gland alveologenesis, controls EMT in both mammary gland development and metastasis. We uncovered this role for Elf5 through analyses of Elf5 conditional knockout animals, various in vitro and in vivo models of EMT and metastasis, an MMTV-neu transgenic model of mammary tumour progression and clinical breast cancer samples. Furthermore, we demonstrate that Elf5 suppresses EMT by directly repressing the transcription of Snail2, a master regulator of mammary stem cells and a known inducer of EMT. These findings establish Elf5 not only as a key cell lineage regulator during normal mammary gland development, but also as a suppressor of EMT and metastasis in breast cancer.

Snail and Twist, transcriptional repressors of E-cadherin as well as inducers of epithelial-mesenchymal transition, play pivotal roles in tumor invasion and metastasis. We investigated the expression of Snail, Twist, and E-cadherin by immunohistochemistry in 193 colorectal cancers, including 79 with positive lymph nodes, 36 with tumor deposits, 39 with both, and 39 with no metastases. Snail was expressed to a greater extent in the group with positive lymph nodes (68.4%), whereas Twist was overexpressed in patients with other metastases (75.0%). Ectopic expression of Snail and Twist correlated with reduced membranous expression of E-cadherin. Importantly, Snail overexpression correlated significantly with lymph node metastasis (P < .0001), whereas Twist up-regulation correlated strongly with other metastases (P < .0001). Multivariate logistic regression analysis showed that Snail was an independent predictor of lymph node metastasis (odds ratio, 4.445; 95% confidence interval, 2.250-8.781; P < .0001), whereas Twist displayed predictive value for metastasis formation (odds ratio, 5.606; 95% confidence interval, 2.829-11.111; P < .0001), suggesting that lymph node and other metastases may follow different signaling pathways. In conclusion, ectopic expression of Snail and Twist contributed to lymph node and disseminated metastasis, respectively, by reducing E-cadherin expression, providing a novel role for Snail and Twist in the progression of colorectal cancer.

PURPOSE: Epithelial-mesenchymal transition (EMT) is a key event in cancer metastasis. This study immunohistochemically examined the expression of EMT-related molecules in both primary colorectal cancer and pulmonary metastases, and analyzed the expression pattern. METHODS: Ten patients with colorectal cancer that underwent surgical resections for both the primary tumor and metastatic pulmonary tumors were included. The expression status of EMT-related molecules was examined using immunohistochemical staining. RESULTS: Nine of the 10 cases maintained the expression of both E-cadherin and beta-catenin in the primary site. The expression of E-cadherin and beta-catenin in the pulmonary metastatic site was preserved in 10 and 12 out of 15 metastatic lesions, respectively. The EMT-related transcription factor, Twist, was positively expressed in all 10 cases, Smad interacting protein 1 (Sip1) in 9, Snail in 4 and Slug in 3 of the primary sites. On the other hand, staining for Twist, Sip1 and Snail at the metastatic pulmonary site, was negative in all 10 cases. CONCLUSION: The expression of EMT-related transcription factors in metastatic pulmonary tumors from colorectal cancer decreased in comparison to the primary tumors. These findings suggested that the expression status of EMT-related transcription factors might play an important role in the implantation of metastatic foci.

FAM3B mRNA has been predicted to have multiple splicing forms. Its secretory form PANDER is decreased in gastric cancers with high invasiveness and metastasis. Here we found that its non-secretory form FAM3B-258 was highly expressed in most colon cancer cell lines and colorectal adenocarcinoma tissues but not hepatocellular carcinoma, lung carcinoma and pancreatic adenocarcinoma cell lines. Elevation of FAM3B-258 was associated with poor cancer cell differentiation. Stable overexpression of FAM3B-258 in colon cancer cells downregulated adhesion proteins, upregulated Slug and Cdc42, promoted cell migration and invasion in vitro and metastasis in nude mice. Slug mediated FAM3B-258-induced downregulation of adhesion molecules, upregulation of Cdc42, and invasion of colon cancer cells. The expression of FAM3B-258 in human colorectal adenocarcinomas was positively correlated with Slug. These results suggest that FAM3B-258 promotes colon cancer cell invasion and metastasis through upregulation of Slug.

Slug and Vimentin genes play a critical role in regulating epithelial-mesenchymal transition (EMT) via downregulation of epithelial markers and upregulation of mesenchymal markers. The present study evaluated the clinical significance of Slug and Vimentin expression as potential disease biomarkers in colorectal cancer (CRC). At first, the biological role of Slug in CRC was assessed by RNA interference in CRC cell lines to assess tumor progression, invasion and migration. Next, we analyzed Slug and Vimentin expression in surgical tissue specimens from 181 CRC patients (Cohort 1) by quantitative real-time reverse transcription-PCR and 208 patients (Cohort 2) by immunohistochemistry. Knockdown of Slug using small interfering RNA in CRC cell lines resulted in inhibition of EMT, reduced cell proliferation, invasion and migration in CRC cells. Interestingly, Slug and Vimentin expression in cancer tissues was significantly higher in patients with higher T stage, lymph node involvement, liver metastasis and advanced tumor node metastasis stages. A significant correlation was observed between Slug and Vimentin expression in CRC (messenger RNA: rho = 0.546, protein: rho = 0.405), and increased expression of Slug and Vimentin was significantly associated with poor prognosis. Furthermore, increased expression of Slug emerged as an independent prognostic factor and a predictive marker of lymph node metastasis in CRC patients. Our data provide novel evidence for the biological and clinical significance of Slug and Vimentin expression as potential predictive biomarkers for identifying patients with lymph node metastasis or poor prognosis in CRC.

PURPOSE: The expression of E-cadherin correlates with the development, progression, and metastasis of esophageal squamous cell carcinoma (ESCC). Slug, a member of the snail family of transcriptional factors, is a newly identified suppressive transcriptional factor of E-cadherin. The purpose of the present study was to evaluate the clinical significance of E-cadherin and Slug expression in ESCC. EXPERIMENTAL DESIGN: Immunohistochemistry was used to investigate the expression of E-cadherin and Slug proteins in 203 patients with ESCC. The relationships between expression of these proteins and clinicopathologic factors, including prognosis, were analyzed. RESULTS: Positive expression of E-cadherin and Slug was observed in 43% and 48% of cases, respectively. The tumors with reduced E-cadherin expression or positive Slug expression invaded deeper, had more lymph node metastasis, and had more lymphatic invasion than the tumors with preserved E-cadherin expression or negative Slug expression. Slug expression significantly correlated with reduced E-cadherin expression. Sixty-seven of the 98 (68.4%) tumors with positive Slug expression had reduced E-cadherin expression (P = 0.0011). Patients with reduced E-cadherin expression or positive Slug expression had poor clinical outcomes. In the preserved E-cadherin group, the 5-year survival rate was better for patients who were negative for Slug expression than for those who were positive for Slug expression (P = 0.035). Multivariate analysis indicated that E-cadherin expression and Slug expression were not independent prognostic factors. CONCLUSIONS: Evaluation of not only the expression of E-cadherin but also the co-expression of E-cadherin and Slug in preserved E-cadherin group is useful for predicting malignant properties of ESCC.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cells in vitro and in vivo in immunodeficient mice. METHODS: We utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assay in vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development. RESULTS: The EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhibited fewer seeded nodes and demonstrated more apoptosis. CONCLUSIONS: Slug down-regulation promotes cell apoptosis and decreases invasion capability in vitro and in vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.

BACKGROUND: The expression of E-cadherin correlates with the progression and metastasis of gastric cancer. Slug, a member of the snail family of transcriptional factors, is a newly identified factor that represses transcription of the E-cadherin gene. The purpose of the present study was to evaluate the clinical significance of E-cadherin and Slug expression in gastric cancer. METHODS: Immunohistochemistry was used to investigate the expression of E-cadherin and Slug proteins in 164 patients with gastric cancer. The relationships between the expression of these proteins and clinicopathological factors, including prognosis, were analyzed. RESULTS: Positive expression of E-cadherin and Slug was observed in 43.9 and 29.9% of cases, respectively. tumors with reduced E-cadherin or positive Slug expression had greater extent of lymph node metastasis, lymphatic invasion, and venous invasion, and were at a worse stage than the tumors with preserved E-cadherin or negative Slug expression. Slug expression was significantly correlated with reduced E-cadherin expression; 37 of the 49 (75.5%) tumors with positive Slug expression had reduced E-cadherin expression (P = 0.0008). Patients with reduced E-cadherin expression or positive Slug expression had poor clinical outcomes. In the group with preserved E-cadherin expression, the 5-year survival rate was better for patients who were negative for Slug expression than for those who were positive for Slug expression (P = 0.0001). However, multivariate analysis indicated that E-cadherin expression and Slug expression were not independent prognostic factors. CONCLUSIONS: Evaluation of not only the expression of E-cadherin, but also the coexpression of E-cadherin and Slug in patients with preserved E-cadherin expression would be useful for predicting malignant properties of gastric cancer.

The ETS family of transcription factors is involved in several physiological and pathological processes including tumor progression. The ETS transcription factors are divided into subfamilies based on the sequence and location of the ETS domain. ETV1 (Ets variant gene 1; also known as ER81), is a member of the PEA3 subfamily, which has been found to promote metastatic progression in several types of human cancer. Previous findings demonstrated that ETV1 expression is upregulated in gastric adenocarcinomas; however, the underlying mechanisms of ETV1-induced metastatic progression in gastric cancer remain elusive. In the present study, we found that the overexpression of ETV1 in normal gastric epithelial cells resulted in epithelial to mesenchymal transition (EMT) and increased invasiveness. Conversely, knockdown of ETV1 resulted in decreased aggressiveness of the invasive gastric cancer cells. Mechanistically, ETV1 transcriptionally upregulates Snail expression. Of note, ETV1 expression is significantly correlated with Snail expression in human gastric tumor samples. In summary, we present data that ETV1 promotes Snail expression to induce EMT-like metastatic progression in gastric cancer.

OBJECTIVE: To explore the expression and clinical significance of Slug, E-cadherin and N-cadherin in gastrointestinal stromal tumors (GIST). METHODS: Seventy eight GIST specimens removed surgically from 2004 to 2007 were collected from the Department of Gastrointestinal Surgery at Guizhou Provincial People's Hospital. There were 48 males and 30 females with an age range of 28 - 87 years old. The expressions of Slug, E-cadherin and N-cadherin in GIST were determined by immunohistochemistry. And the correlations with their clinicopathologic characteristics were analyzed. RESULTS: The positive rates of Slug, E-cadherin and N-cadherin in GIST were 53.8% (42/78), 35.9% (28/78) and 75.6% (59/78) respectively. And the differences were statistically significant (chi(2) = 24.98, P < 0.05). Slug was expressed markedly higher in the cases of GIST with distant metastasis or distant metastasis and local invasion: 75% (18/24) vs 44.4% (24/54), 63.6% (28/44) vs 41.2% (14/34), both P < 0.05. And E-cadherin was expressed markedly lower in the cases of GIST with distant metastasis: 16.7% (4/24) vs 44.4% (24/54), P < 0.05. The expression of N-cadherin was not significantly different between its clinicopathological characteristics (allP > 0.05). The expression of Slug correlated negatively with that of E-cadherin (r(s) = -0.267, P = 0.018). But it had no correlation with that of N-cadherin (r(s) = 0.056, P = 0.625). CONCLUSION: Slug is expressed markedly higher while E-cadherin markedly lower in metastatic GIST, and both are closely correlated with the metastasis of GIST.

AIM: To explore the expression and function of slug, a transcriptional repressor, in human intrahepatic cholangiocarcinoma (IHCC) and identify its role in IHCC progression. METHODS: expression of slug was detected in 36 cases of IHCC and 12 cases of normal intrahepatic bile ducts and liver parenchyma by immunohistochemistry. The patients were divided into low slug expression group (< 20% of carcinoma cells stained) and high slug expression group (> or = 20% of carcinoma cells stained). Slug expression was correlated with clinicopathological parameters of IHCC patients. The patients were defined as short-term survivors if their survival time was < 12 mo and as long-term survivors if their survival time was > or = 12 mo. RESULTS: Slug was not expressed in normal liver epithelium samples, lowly expressed in 15 tissue samples (10 -, 5 +) and highly expressed in 21 tissue samples (16 ++; 5 +++) from IHCC patients. The survival rate of patients with a low slug expression was 33.3% (n = 5) and 66.7% (n = 10), respectively. The survival rate of patients with a high slug expression was 61.9% (n = 13) and 38.1% (n = 8), respectively (P = 0.02). Lymph node metastasis was found in 4 (26.7%) out of the 15 patients with a low slug expression and in 14 (66.7%) out of the 21 patients with a high slug expression, respectively. The incidence rate of lymph node metastasis increased with the increasing slug expression level (P = 0.003), and higher in patients with a high slug expression than in those with a low slug expression. Slug expression did not significantly correlate with the tumor size and stage or histologic grade, or with the gender and age of patients CONCLUSION: Slug expression is a novel prognostic marker for IHCC with lymph node metastasis.

OBJECTIVE: Lung cancer is a deadly cancer, whose kills more people worldwide than any other malignancy. SLUG (SNAI2, Snail2) is involved in the epithelial mesenchymal transition in physiological and in pathological contexts and is implicated in the development and progression of lung cancer. METHODS: We constructed a lentivirus vector with SLUG shRNA (LV-shSLUG). LV-shSLUG and a control lentivirus were infected into the non-small cell lung cancer cell A549 and real-time PCR, Western blot and IHC were applied to assess expression of the SLUG gene. Cell proliferation and migration were detected using MTT and clony formation methods. RESULTS: Real-time PCR, Western Blot and IHC results confirmed down-regulation of SLUG expression by its shRNA by about 80%~90% at both the mRNA and protein levels. Knockdown of SLUG significantly suppressed lung cancer cell proliferation. Furthermore, knockdown of SLUG significantly inhibited lung cancer cell invasion and metastasis. Finally, knockdown of SLUG induced the down-regulation of Bcl-2 and up-regulation of E-cadherin. CONCLUSION: These results indicate that SLUG is a newly identified gene associated with lung cancer growth and metastasis. SLUG may serve as a new therapeutic target for the treatment of lung cancer in the future.

TGF-beta promotes tumor invasion and metastasis by inducing an epithelial-mesenchymal transition (EMT). Understanding the molecular and epigenetic mechanisms by which TGF-beta induces EMT may facilitate the development of new therapeutic strategies for metastasis. Here, we report that TGF-beta induced SNAI2 to promote EMT by repressing miR-203. Although miR-203 targeted SNAI2, SNAI2 induced by TGF-beta could directly bind to the miR-203 promoter to inhibit its transcription. SNAI2 and miR-203 formed a double negative feedback loop to inhibit each other's expression, thereby controlling EMT. Moreover, we found that miR-203 was significantly down-regulated in highly metastatic breast cancer cells. The restoration of miR-203 in highly metastatic breast cancer cells inhibited tumor cell invasion in vitro and lung metastatic colonization in vivo by repressing SNAI2. Taken together, our results suggest that the SNAI2 and miR-203 regulatory loop plays important roles in EMT and tumor metastasis.

BACKGROUND: It has been reported that zinc-finger transcription factor Slug plays a critical role in tumor proliferation and differentiation, relapse, invasion, metastasis, and decreased survival. However, there is little information on the expression and role of Slug in salivary adenoid cystic carcinoma (ACC). METHOD: Demographic variables and primary tumor site, dates of diagnoses, perineural invasion, local regional recurrence, and distant metastasis of 121 cases of salivary ACC treated at the Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University between 1996 and 2005 were retrieved. The Slug expression of all these cases was examined by immunohistochemical methods. The association between Slug expression and clinicopathological variables was analyzed using Chi-squared test, and the prognostic factors were examined by univariate and multivariate analyses. RESULTS: Our data demonstrated that the positive expression of Slug was observed in 71.90% (87/121) of cases. Slug expression was significantly associated with tumor site, TNM stage, histological pattern, perineural invasion, local regional recurrence and distant metastasis of patients with ACC (P<0.05). And Slug expression, local regional recurrence and distant metastasis were independent and significant prognostic factors in all patients. CONCLUSIONS: It is proposed that Slug may play an important role in the invasion and metastasis of ACC, and that Slug had the potential for one of the strong invasion and metastasis indicators at presentation of ACC patients.

Hypoxia inducible factor-1alpha (HIF-1alpha) is upregulated by hypoxia, and involved in tumor growth and metastasis in many malignant tumors including papillary thyroid carcinoma (PTC). Metallothionein (MT) is a group of small molecular weight cysteine-rich proteins with a broad variety of functions. SLUG is a member of SNAIL superfamily of zinc finger transcriptional factors implicated in epithelial-mesenchymal transition (EMT). The purpose of this study was to examine HIF-1alpha, MT and SLUG expression in PTC and assess association of their expression with clinicopathological indicators. HIF-1alpha, MT and SLUG protein expression in 129 PTCs, 61 nodular hyperplasia and 118 normal thyroid tissue specimens were analyzed using immunohistochemistry. The protein expression levels of these three molecules were up-regulated in PTCs. High protein expression of HIF-1alpha, MT and SLUG was significantly correlated with high TNM stage (P=0.003, 0.002, 0.024, respectively) and lymph node metastasis (LNM) (P<0.001 for all three molecules). Furthermore, HIF-1alpha, MT and SLUG protein expression were correlated with one another. Concomitant high expression of any two of these three molecules had stronger correlation with high TNM stage (Pexpression of all these three molecules is significantly associated with high TNM stage and LNM as compared with cases not showing such expression (P<0.001). These results demonstrated that the evaluation of HIF-1alpha, MT and SLUG expression in PTC may be useful in predicting the risk of LNM and high TNM stage.

The members of the Snail superfamily of zinc-finger transcription factors, including Snai1 and Snai2, are involved in essential biological processes, such as epithelial-mesenchymal transition (EMT). Although Snai1 has been investigated in a number of cancers, our knowledge on Snai2 and its role(s) in squamous cell carcinoma of oral tongue (SCCOT) is limited. In this study, we confirmed the previous observation that over-expression of Snai2 is a frequent event in SCCOT. We further demonstrated that Snai2 over-expression is associated with lymph node metastasis in two independent SCCOT patient cohorts (total n = 129). Statistical analysis revealed that Snai2 over-expression was correlated with reduced overall survival. Furthermore, over-expression of Snai2 was correlated with reduced E-cadherin expression and enhanced Vimentin expression, suggesting a functional role of Snai2 in EMT. These observations were confirmed in vitro, in which knockdown of Snai2 induced a switch from a mesenchymal-like morphology to an epithelial-like morphology in SCCOT cell lines, and suppressed the cell invasion and migration. In contrast, ectopic transfection of Snai2 led to enhanced cell invasion and migration. Furthermore, Snai2 knockdown attenuated TGFbeta1-induced EMT in SCCOT cell lines. Taken together, these data suggest that Snai2 plays major roles in EMT and the progression of SCCOT and may serve as a therapeutic target for patients at risk of metastasis.