Stomatin-like Protein 2 Expression Research Articles

STOML2 restricts mitophagy and increases chemosensitivity in pancreatic cancer through stabilizing PARL-induced PINK1 degradation

Pancreatic cancer remains one of the most lethal diseases with a relatively low 5-year survival rate, and gemcitabine-based chemoresistance occurs constantly. Mitochondria, as the power factory in cancer cells, are involved in the process of chemoresistance. The dynamic balance of mitochondria is under the control of mitophagy. Stomatin-like protein 2 (STOML2) is located in the mitochondrial inner membrane and is highly expressed in cancer cells. In this study, using a tissue microarray (TMA), we found that high STOML2 expression was correlated with higher survival of patients with pancreatic cancer. Meanwhile, the proliferation and chemoresistance of pancreatic cancer cells could be retarded by STOML2. In addition, we found that STOML2 was positively related to mitochondrial mass and negatively related to mitophagy in pancreatic cancer cells. STOML2 stabilized PARL and further prevented gemcitabine-induced PINK1-dependent mitophagy. We also generated subcutaneous xenografts to verify the enhancement of gemcitabine therapy induced by STOML2. These findings suggested that STOML2 regulated the mitophagy process through the PARL/PINK1 pathway, thereby reducing the chemoresistance of pancreatic cancer. STOML2-overexpression targeted therapy might be helpful for gemcitabine sensitization in the future.

Stomatin-like protein 2 deficiency exacerbates adverse cardiac remodeling

Myocardial fibrosis, oxidative stress, and autophagy both play key roles in the progression of adverse cardiac remodeling. Stomatin-like protein 2 (SLP-2) is closely related to mitochondrial function, but little is known about its role and mechanism in cardiac remodeling. We developed doxorubicin (Dox), angiotensin (Ang) II, and myocardial ischemia-reperfusion (I/R) injury induced cardiac remodeling model and Dox treated H9C2 cell injury model using SLP-2 knockout (SLP-2-/-) mice and H9C2 cells with low SLP-2 expression. We first examined cardiac functional and structural changes as well as levels of oxidative stress, apoptosis and autophagy. We found that SLP-2 deficiency leads to decreased cardiac function and promotes myocardial fibrosis. After Dox and Ang II treatment, SLP-2 deficiency further aggravated myocardial fibrosis, increased myocardial oxidative stress and apoptosis, and activated autophagy by inhibiting PI3K-Akt-mTOR signaling pathway, ultimately exacerbating adverse cardiac remodeling. Similarly, SLP-2 deficiency further exacerbates adverse cardiac remodeling after myocardial I/R injury. Moreover, we extracted cardiomyocyte mitochondria for proteomic analysis, suggesting that SLP-2 deficiency may be involved in myocardial I/R injury induced adverse cardiac remodeling by influencing ubiquitination of intramitochondrial proteins. In addition, the oxidative stress, apoptosis and autophagy levels of H9C2 cells with low SLP-2 expression were further enhanced, and the PI3K-Akt-mTOR signaling pathway was further inhibited under Dox stimulation. Our results suggest that SLP-2 deficiency promotes myocardial fibrosis, disrupts normal mitochondrial function, overactivates autophagy via PI3K-Akt-mTOR signaling pathway, affects the level of ubiquitination, leads to irreversible myocardial damage, and ultimately exacerbates adverse cardiac remodeling.

SLP-2 regulates the generation of reactive oxygen species and the ERK pathway to promote papillary thyroid carcinoma motility and angiogenesis

Although papillary thyroid cancer (PTC) has a generally decent prognosis, approximately 10% of patients experience recurrence, which is frequently associated with distant metastasis. Stomatin-like protein 2 (SLP-2), a protein located in the mitochondrial intermembrane space, is thought to be a possible cancer promoter. This study aimed to discover the involvement of SLP-2 in PTC motility and angiogenesis, and to initially explore its mechanism. According to the CCLE database, SLP-2 was universally increased in various cancers. Then SLP-2 expression in PTC cell lines was evaluated. Thereafter the influences of SLP-2 knockdown on cell migration, invasion, epithelial-mesenchymal transition (EMT), and angiogenesis were assessed, respectively. The mediated roles of reactive oxygen species (ROS) and MAPKs in the SLP-2 regulation were likewise determined. SLP-2 was discovered to be upregulated in PTC cells, and its knockdown could suppress cell migration, invasion, EMT, and angiogenesis. Declined SLP-2 expression also facilitated ROS generation and inhibited phosphorylation of MAPKs. Moreover, ERK agonist and ROS scavenger treatment partially reversed the impacts of SLP-2 knockdown on cells, indicating SLP-2 regulated generation of ROS and ERK pathway to promote PTC motility and angiogenesis. Generally, SLP-2 appears to be one of the major genes in the pathogenesis of PTC. Silencing its expression may have an impact on the onset and evolution of PTC. The fact that SLP-2 has a considerable influence on ROS levels implies that PTC can be treated by boosting ROS levels.

Stomatin-like Protein 2 Promotes Tumor Cell Survival by Activating the JAK2-STAT3-PIM1 Pathway, Suggesting a Novel Therapy in CRC

Despite intensive efforts, a considerable proportion of colorectal cancer (CRC) patients develop local recurrence and distant metastasis. Stomatin-like protein 2 (SLP-2), a member of the highly conserved stomatin superfamily, is upregulated across cancer types. However, the biological and functional roles of SLP-2 remain elusive in CRC. Here, we report that high SLP-2 expression was found in CRC tissues and was linked to tumor progression and tumor cell differentiation. Additionally, high SLP-2 expression correlated with poor overall survival (OS) in CRC patients (p < 0.001). SLP-2 knockout (SLP-2KO), generated by CRISPR/Cas9, reduced cell growth, migration, and invasion; induced apoptosis in CRC cells; and reduced tumor xenograft growth in vivo. A 181-compound library screening showed that SLP-2KO produced resistance to JAK2 inhibitors (NVP-BSK805 and TG-101348) and a PIM1 inhibitor (SGI-1776), revealing that the JAK2-STAT3-PIM1 oncogenic pathway was potentially controlled by SLP-2 in CRC. In vitro and in vivo, TG-101348 combined with SGI-1776 was synergistic in CRC (combination index [CI] < 1). Overall, our findings suggest that SLP-2 controls the JAK2-STAT3-PIM1 oncogenic pathway, offering a rationale for a novel therapeutic strategy with combined SGI-1776 and TG-101348 in CRC. Additionally, SLP-2 may be a prognostic marker and biomarker for sensitivity to JAK2 and PIM1 inhibitors.

Clinical significance of SLP-2 in epithelial ovarian cancer and its regulatory effect on the Notch signaling pathway.

To explore the expression of Stomatin-like protein 2 (SLP-2) and its clinical significance in epithelial ovarian cancer (EOC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the differential expression of SLP-2 in EOC tissues and cell lines. The relationship between SLP-2 expression and clinical pathological data of EOC patients was analyzed. QRT-PCR results suggested that the SLP-2 was up-regulated in both EOC tissues and EOC cells by comparing with normal control. SLP-2 expression was a correlation with tumor pathological grade, distant metastasis, and TNM stage in EOC patients. Down-regulation of SLP-2 could significantly inhibit proliferation and promote apoptosis of EOC cells by activating the Notch signaling pathway. Knockdown of SLP-2 markedly downregulated Notch1 and Hes1. SLP-2 was a novel factor involved in EOC progression, and could be utilized as a potential biomarker and therapeutic target for the EOC patients.

Stomatin-like protein-2 confers neuroprotection effect in oxygen-glucose deprivation/reoxygenation-injured neurons by regulating AMPK/Nrf2 signalling

Stomatin-like protein-2 (SLP-2) has emerged as a cytoprotective protein that confers a protective effect against various stresses. However, whether SLP-2 confers neuroprotection during cerebral ischemia/reperfusion injury remains unclear. In the present study, we investigated the role of SLP-2 in regulating oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis and oxidative stress, which has been used as an in vitro model of cerebral ischemia/reperfusion injury. We found that OGD/R treatment resulted in a significant reduction in SLP-2 expression in neurons. Functional experiments demonstrated that SLP-2 overexpression significantly increased cell viability and decreased cell apoptosis and reactive oxygen species (ROS) production in OGD/R-exposed neurons, while SLP-2 inhibition showed the opposite effect. Notably, SLP-2 overexpression was shown to up-regulate the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). In addition, SLP-2 overexpression increased the nuclear expression of nuclear factor (erythroid-derived 2)-like 2 and reinforced the activity of Nrf2/antioxidant response element (ARE)-mediated transcription. However, AMPK inhibition or Nrf2/ARE inhibition partially reversed SLP-2-mediated neuroprotection effect in OGD/R-exposed neurons. Taken together, these results demonstrate that SLP-2 confers neuroprotection effect in OGD/R-injured neurons associated with reinforcing AMPK/Nrf2 signalling, suggesting SLP-2 as a potential therapeutic target for cerebral ischemia/reperfusion injury.

Enhanced SLP-2 promotes invasion and metastasis by regulating Wnt/β-catenin signal pathway in colorectal cancer and predicts poor prognosis

Stomatin-like protein-2 (SLP-2) gene belongs to the stomatin supergene family, and previous studies have revealed up-regulated SLP-2 expression in gallbladder cancer, lung cancer, and esophageal cancer, while the role of SLP-2 in colorectal cancer (CRC) remains unclear and needs further investigation. Therefore, the expression levels of SLP-2 in CRC tissue and cell lines were tested in this study. Besides, we further explored the role of SLP-2 in CRC invasion and metastasis at molecular level via gene intervention technique. Our results demonstrated that the positive rate of SLP-2 expression in CRC tissues was higher than that in the adjacent non-cancerous tissues (P < 0.05); positive SLP-2 expression predicted poorer prognosis of CRC patients as an independent risk factor (P < 0.05). Cell activities and the capacity of migration and invasion significantly decreased after the suppression of SLP-2 in SW620 cells (P < 0.05). Furthermore, the suppression of SLP-2 in SW620 cells resulted in varieties of invasion and metastasis-related genes and Wnt/β-catenin signal pathway (P < 0.05). The present study identified that SLP-2 may predict a poor prognosis in CRC patients as a novel marker, and SLP-2 may facilitate the migration and invasion of CRC via regulating Wnt/β-catenin pathway activities.

Stomatin-like protein 2 regulates survivin expression in non-small cell lung cancer cells through \u03b2-catenin signaling pathway

The overexpression of stomatin-like protein-2 (SLP-2) is commonly observed in non-small cell lung cancer (NSCLC) cells. In the present study, we transfected a number of NSCLC cells with an SLP-2 shRNA-expressing vector (AdSLP2i) and examined its possible effects on cell growth and apoptosis. We found that suppression of SLP-2 expression inhibited cell growth, and that the apoptosis induced by SLP-2 suppression was correlated with decreased survivin protein expression. Moreover, the reduced survivin expression was found to be associated with reduced β-catenin nuclear localization and appeared not to be modulated through the AKT signaling pathway. By using immunoprecipitation and proteomics to analyze protein–protein interactions in A549 cells with SLP-2 overexpression, we found that annexin A2 interacted with SLP-2 and β-catenin directly. Our data further suggested that the knockdown of SLP-2 gene affected the SLP-2/Annexin A2/β-catenin cascade formation, reduced the translocation of cytoplasmic β-catenin into nucleus, and downregulated downstream target genes. The results presented in this study, together with our previous findings, suggest that SLP-2 promotes NSCLC cell proliferation by enhancing survivin expression mediated via β-catenin pathway.

Stomatin-like protein 2 is overexpressed in cervical cancer and involved in tumor cell apoptosis.

Stomatin-like protein 2 (SLP-2) is overexpressed in numerous types of human cancer and previous studies revealed that SLP-2 may function in mitochondria. The purpose of the present study was to evaluate the expression of SLP-2 in cervical cancer and the association between SLP-2 expression and clinical features, in addition to investigating the role of SLP-2 in the apoptosis of cervical cancer cells. The expression profile of SLP-2 was determined by quantitative polymerase chain reaction, western blotting and immunohistochemical staining. The effect of SLP-2 on cell apoptosis induced by chemotherapeutics in cervical cancer cells was evaluated using Annexin V staining and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assays. The results indicated that SLP-2 expression in cervical cancer was significantly upregulated at the mRNA and protein levels, compared with that in normal cervical tissues. Immunohistochemical analysis revealed significant correlation between SLP-2 protein expression and clinical characteristics, including the squamous cell carcinoma antigen (P=0.003), deep stromal invasion (P=0.021), lymphovascular space involvement (P=0.044) and pelvic lymph node metastasis (P<0.001), which served as independent prognostic factors for predicting the shortening of overall survival time in patients with early-stage cervical cancer. In addition, TUNEL and Annexin V binding assays revealed that silencing SLP-2 expression significantly enhanced the sensitivity of cervical cancer cells to apoptosis induced by chemotherapeutics. Taken together, the results of the present study suggest that SLP-2 may be a progressive gene in the development of cervical cancer. Overexpression of SLP-2 serves an important role in the apoptosis of human cervical cancer cells.

The mechanism of stomatin-like protein 2 gene regulating Wnt/β-catenin signaling pathway on proliferation and apoptosis of gastric cancer cells

Objective To investigate the effect of stomatin-like protein 2 (SLP-2) gene on the proliferation and apoptosis of gastric cancer cells by Wnt/β-catenin signaling pathway. Methods The expression of SLP-2 gene in human gastric cancer tissues was detected by Western blotting; NC-siRNA, SLP-2-siRNA1 and SLP-2-siRNA2 were transfected into human gastric cancer SGC-7901 cells, and not transfected with any siRNA as the control group; the expression of SLP-2 protein after transfected cells was detected by Western blotting; cells transfected for 48 h, cell apoptosis was detected by flow cytometry; Cleaved Caspase-3, β-catenin, c-Myc, Cyclin D1protein expression was detected by Western blotting. Results The expression of SLP-2 protein in gastric carcinoma (0.283±0.016)was significantly higher than paracancerous tissues (0.082±0.016), (t=7.789, P=0.003); the inhibitory effect of SLP-2-siRNA2 group was more obvious, and was choiced as a follow-up study; the apoptosis rate (16.62±1.32)% of cells and Cleaved Caspase-3 (1.421±0.210) protein expression in SLP-2-siRNA group were significantly higher than the control group (1.56±0.56)%, (0.510±0.083), β-catenin (0.157±0.024), (0.039±0.016), Cyclin D1 (0.052±0.012) protein expression was significantly lower than the control group (0.311±0.036, 0.137±0.026, 0.183±0.021) (tapoptosis rate=9.324, Papoptosis rate=0.001; tCleaved Caspase-3=6.112, PCleaved Caspase-3=0.006; tβ-catenin=8.868, Pβ-catenin=0.003; tc-Myc=9.112, Pc-Myc=0.002; tCyclin D1=9.987, PCyclin D1=0.001). Conclusion SLP-2 is highly expressed in gastric cancer, Silencing SLP-2 expression can inhibit the proliferation and apoptosis of human gastric cancer cell line SGC-7901, and its mechanism is related to the regulation of Wnt/β-catenin signaling pathway. Key words: Stomatin-like protein 2; Wnt/β-catenin signaling pathway; Gastric cancer; Proliferation; Apoptosis

Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation.

Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p < 0.001), pT status (p < 0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients.

Increased expression of stomatin-like protein 2 (STOML2) predicts decreased survival in gastric adenocarcinoma: a retrospective study

Stomatin-like protein 2 (STOML2), a member of the stomatin, has been reported to be upregulated in several human cancers. However, its role and clinical significance in gastric adenocarcinoma remains unclear to date. The purpose of this retrospective study was to explore whether there was a correlation between the expression of STOML2 by immunohistochemistry and the clinical outcome of a large group of patients with gastric adenocarcinoma. In this retrospective study, we performed immunohistochemistry to evaluation of STOML2 expression in a large panel of gastric adenocarcinoma samples. The receiver operating characteristic method was used to define the STOML2 immunoreactivity score cutoff value. The clinical/prognostic significance of STOML2 expression was analyzed statistically. Kaplan-Meier analysis was used to compare the postoperative survival between groups. STOML2 was overexpressed in gastric cancer compared with paracancerous normal mucosa. Increased STOML2 expression was associated with higher histologic grade (P = 0.047), T category (P < 0.001), and N category (P = 0.01). Patients with high expression of STOML2 demonstrated shortened overall survival compared with those with low expression of STOML2 (median of 38.9 vs. 64.0 months, P < 0.001). Furthermore, STOML2 expression could stratify patients survival in stage N0 (P < 0.001). Multivariate analysis showed that the level of STOML2 expression was an independent prognostic factor in gastric adenocarcinoma (RR = 1.920, P = 0.001). Increased expression of STOML2 suggests unfavorable prognosis for gastric adenocarcinoma patients. Further studies are warranted.

Stomatin-like protein 2 is associated with the clinicopathological features of human papillary thyroid cancer and is regulated by TGF-β in thyroid cancer cells

Papillary thyroid cancer (PTC) accounts for 80-90% of all cases of thyroid malignancies. Stomatin-like protein 2 (SLP-2) is a novel member of the stomatin superfamily and is found in several types of human tumors. However, whether it is expressed in human PTC is unknown. In the present study, we aimed to explore the diagnostic value of SLP-2 in patients with PTC and to investigate whether SLP-2 expression is regulated by transforming growth factor-β (TGF-β), a cytokine which plays an important role in PTC tumorigenesis. A total of 107 patients consisting of 99 cases of classical and 8 cases of follicular variant PTC was examined. The expression of SLP-2 mRNA and protein was examined by immunohistochemistry (IHC) and qPCR, respectively. We found that SLP-2 was overexpressed in human PTC. The expression of SLP-2 was significantly associated with clinicopathological features of the PTC cases. Particularly, increased SLP-2 expression was mainly correlated with primary tumors >1 cm in size, with late stage tumors and with metastatic lymph nodes. The expression of SLP-2 was correlated with the expression of Ki-67, a cell proliferation marker, in PTC tissues as detected by IHC. SLP-2 was upregulated by TGF-β1 in PTC cells as evaluated by western blotting. The present data revealed for the first time that patients with PTC exhibited SLP-2 overexpression that was associated with clinicopathological features. The correlation between SLP-2 expression and proliferation marker Ki-67 may be characteristic of PTC and may reflect PTC progression. SLP-2 was upregulated by TGF-β1, indicating a possible role of SLP-2 in PTC tumorigenesis. Our data suggest that SLP-2 may be considered as a useful diagnostic marker and therapeutic target for PTC.

Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer

Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P = 0.019), clinical stage (P = 0.001), and lymph node metastasis (P = 0.026). The Kaplan-Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.

Expression of SLP-2 Was Associated with Invasion of Esophageal Squamous Cell Carcinoma

IntroductionStomatin-like protein 2 (SLP-2), a member of the Stomatin superfamily, has been identified as an oncogenic-related protein and found to be up-regulated in multi-cancers. Nonetheless, the expression pattern and regulation of SLP-2 in human esophageal squamous cell carcinoma (ESCC) remain unexplored.MethodsImmunohistochemistry and immunofluorescence staining analysis were performed to show SLP-2 expression and location. RNAi method was used to inhibit specific protein expression. Transwell assay was done to investigate cells invasive capability. RT-PCR and Western blot analysis were used to detect mRNA and protein expression levels.ResultsImmunohistochemical analysis showed that up-regulation of SLP-2 was found in invasive front compared with cancer central tissue in ESCC. Inhibition of SLP-2 by SLP-2 siRNA can decrease ESCC cells invasive capability through MMP-2 dependent manner. Up-regulation of SLP-2 was effectively abrogated by the ERK1/2 inhibitors either PD98059 or U0126, but no effect was showed by the treatment of AKT inhibitors either LY294002 or MK-2206. So the regulation of SLP-2 was involved in activation of the MAPK/ERK pathway.ConclusionsWe found that PMA/EGF could induce the up-regulated expression of SLP-2 probably through activating ERK signalling. The current study suggests that SLP-2 may represent an important molecular hallmark that is clinically relevant to the invasion of ESCC.

Increased levels of SLP-2 correlate with poor prognosis in gastric cancer

Stomatin-like protein 2 (SLP-2) is a member of the highly conserved stomatin protein family whose homologues span from Archaea to humans and include stomatin, SLP-1, and SLP-3. Several studies have indicated that overexpression of SLP-2 is strongly associated with adhesion and migration in several human cancers. The aim of the present study was to evaluate SLP-2 expression at the mRNA and protein level in patients with gastric cancer (GC) and to examine the relationships between SLP-2 expression, clinicopathological features, and prognosis. We investigated SLP-2 expression in primary GC and paired normal gastric tissue by real-time PCR (RT-PCR; n = 16) and Western blot analysis (n = 32). Additionally, we performed immunohistochemistry (IHC) on 113 paraffin-embedded GC specimens, 30 matched normal specimens, and 30 paired metastatic lymph node samples. SLP-2 is overexpressed in GC compared with the adjacent normal gastric epithelium (p < 0.001), and high-level SLP-2 expression is significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Furthermore, elevated SLP-2 expression is an independent prognostic factor in multivariate analysis using the Cox regression model (p = 0.005). Overexpression of SLP-2 may contribute to the progression and poor prognosis of GC.

Knockdown of stomatin‐like protein 2 (STOML2) reduces the invasive ability of glioma cells through inhibition of the NF‐κB/MMP‐9 pathway

Stomatin-like protein 2 (STOML2), a member of the stomatin family, has been reported to be up-regulated in several types of human cancers. The clinical significance and biological role of STOML2 in gliomas remain largely unknown. Here, we describe the significantly up-regulated expression of STOML2 in glioma cell lines and glioma tissues at both the transcriptional and translational levels. Silencing endogenous STOML2 in glioma cells and primary glioma cells drastically reduced their migratory speed and invasive ability, associated with induction of matrix metallopeptidase 9 (MMP-9). We also demonstrated that knockdown of STOML2 significantly inhibited the transcriptional activity of NF-κB and repressed the expression levels of NF-κB target genes, including MMP-9. A luciferase reporter assay revealed that the impact of STOML2 on MMP-9 expression is NF-κB-dependent. Immunohistochemical analysis showed that the up-regulation of STOML2 was significantly correlated with the WHO histological grade of gliomas (p < 0.001). Patients with higher STOML2 expression levels had an overall shorter survival time, whereas patients with lower expression of STOML2 had a longer survival time. A multivariate analysis revealed that STOML2 expression might be an independent prognostic indicator for the survival of glioma patients. Taken together, our results suggest that overexpression of STOML2 is associated with glioma aggressiveness and may represent an independent prognostic factor for the outcome of glioma patients.

Expression of SLP-2 protein in esophageal squamous cell carcinoma is associated with cancer invasion

To study the expression of stomatin-like protein-2 (SLP-2) in esophageal squamous cell carcinoma (ESCC), and analyze the correlation between SLP-2 expression and clinicopathological features. The expression of SLP-2 protein in ESCC tissues (18 and 220 cases respectively) was detected by Western blot and IHC. The association between SLP-2 expression and clinicopathological features was analyzed. Compared with normal epithelium, 13 cases of ESCC tissues showed a higher expression of SLP-2 on the protein level (72.2%, 13/18). IHC analysis on tissue microarray revealed that the expression rate of SLP-2 protein in ESCC was 54.1% and in normal esophageal mucosa was 3.6%, showing a significant difference (P < 0.001). SLP-2 high-level expression correlates with the extent of ESCC invasion (P = 0.033), but not with other clinicopathologic characteristics (P > 0.05). SLP-2 as a novel cancer-related gene may play an important role in tumorigenesis of ESCC. The overexpression of SLP-2 may be closely associated with the invasion of esophageal cancer.

Relationship between SLP-2 expression and prognosis in laryngeal squamous cell carcinoma and mammary invasive carcinoma

To study the expression of stomatin like protein-2 (SLP-2) at mRNA and protein levels in two kinds of malignant epithelial tumors, including laryngeal squamous cell carcinoma (LSCC) and invasive breast cancer, and to study the relations of SLP-2 expression and clinicopathologic parameters with the prognosis. RT-PCR and Western blot were used to detect the expression of SLP-2 mRNA and protein in LSCC and their normal counterparts (46 and 10 pair, respectively). Immunohistochemistry was carried on tissue array constructed from LSCC (104 cases) and breast cancer (263 cases), respectively. The association between SLP-2 expression and clinicopathologic parameters was analyzed. LSCC showed a higher expression of SLP-2 than that of their normal counterparts (negative expression) at mRNA (83%, 38/46) and protein (7/10) level. Immunohistochemical analysis of LSCC showed that compared with negative expression in normal laryngeal epithelium (0/20), a higher SLP-2 expression was detected in LSCC (36/104, P=0.000) and associated with the advanced clinical stage (P<0.01) and lymph node metastasis (P=0.003). Immunohistochemical study of invasive breast cancer demonstrated that compared with negative expression in normal breast tissue (0/10), more than one half of the cases showed a high SLP-2 expression (52.5%, 138/263, P=0.000) in breast cancer, which correlated with the tumor size (P=0.020), lymph node metastasis (P<0.01), advanced clinical stage (P<0.01), distant metastasis (P=0.002) and HER2/neu protein expression (P=0.037). Survival analysis showed a shorter overall survival probability in patients with a high SLP-2 expression. It was considered that lymph node metastasis, positive HER2/neu expression, and high-level SLP-2 expression may act as the independent prognostic factors for those tumors. A high expression level of SLP-2 may be associating with the development of invasion and metastasis in LSCC and breast cancer, and SLP-2 is also considered working as an independent factor indicating a poor prognosis clinically in breast cancer.

SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma

Objective: To investigate the role of stomatin-like protein 2 (SLP-2), a novel cancer-related gene, in pulmonary squamous cell carcinoma (PSCC) and its implications.Methods: Immunohistochemical detection of SLP-2 was performed on 96 cases of PSCC with a tissue microarray.Results: SLP-2 was overexpressed in lung cancer compared with normal lung tissue (p <0.001). High-level SLP-2 expression was significantly correlated with distant metastasis (p = 0.025), decreased overall survival (p = 0.018) and disease-free survival (p = 0.017). SLP-2 overexpression was an independent prognostic factor in multivariate analysis using the Cox regression model (p <0.05).Conclusion: SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in PSCC. SLP-2 could be regarded as a new significant prognostic biomarker for patients with PSCC.