The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis.

Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is a powerful transcription factor that acts dual roles in gene activation and repression. High expression level of YY1 has been reported in CRC, indicating the existence of stable factors of YY1 in CRC cells. We aimed to identify the key molecules and underlying mechanisms responsible for stabilizing YY1 expression in CRC. Mass spectrometry analysis was utilized to identify USP7 as a potential molecule that interacted with YY1. Mechanically, USP7 stabilizes YY1 expression at the protein level by interfering its K63 linkage ubiquitination. YY1 exerts its oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, at the pathological level, there is a positive correlation between the expression of YY1 and the budding of CRC. This study has revealed the intricate interplay between YY1 and USP7 in CRC, suggesting that they could serve as novel therapeutic targets or predictive biomarkers for CRC patients.

LncRNA LINC00460 facilitates the proliferation and metastasis of renal cell carcinoma via PI3K/AKT signaling pathway.

Renal cell carcinoma (RCC) is one of the most prevalent cancers diseases in the worldwide. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. LINC00460 has been reported to participate in many kinds of malignancies and promotes cancer progressions. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to explore the potential function and regulation mechanism of LINC00460 in RCC. We analysed the LINC00460 expression and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases. LINC00460 level in normal renal cell line and RCC cell lines were examined by qRT-PCR. We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression of LINC00460 both in RCC tissues and cell. RCC patients with elevated LINC00460 expression have shorter survival. Up-expression of LINC00460 promoted cell proliferation, invasion and migration, meanwhile down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study showed that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT.

SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT.

OBJECTIVE: Serine hydroxymethyltransferase 2 (SHMT2) is the first rate-limiting enzyme for serine/glycine biosynthesis and one carbon metabolism. Here, we explore the underlying mechanism of how SHMT2 functions in renal cell carcinoma (RCC) initiation. METHODS: In this study, SHMT2 expression was assessed in RCC tissues. In vitro experiments were performed to investigate the functional role of SHMT2. The detailed mechanisms of SHMT2-mediated PPAT were addressed. RESULTS: Increased SHMT2 facilitated RCC cell proliferation by inducing the G1/S phase transition. And SHMT2 promoted the expression of PPAT. Mechanism dissection revealed that SHMT2 enhanced the m6A modification through the endogenous methyl donor SAM mediated by SHMT2 via serine/glycine one carbon metabolic networks. SHMT2-catalyzed serine/glycine conversion regulated PPAT expression in an m6A-IGF2BP2-dependent manner. SHMT2 promoted RCC cell proliferation by upregulating PPAT expression. CONCLUSIONS: SHMT2 promotes RCC tumorigenesis by increasing PPAT expression. Thus, SHMT2 may be a novel potential therapeutic target for RCC.

Role of Circular RNA in Kidney-Related Diseases.

The kidney is vital in maintaining fluid, electrolyte, and acid-base balance. Kidney-related diseases, which are an increasing public health issue, can happen to people of any age and at any time. Circular RNAs (circRNAs) are endogenous RNA that are produced by selective RNA splicing and are involved in progression of various diseases. Studies have shown that various kidney diseases, including renal cell carcinoma, acute kidney injury, and chronic kidney disease, are linked to circRNAs. This review outlines the characteristics and biological functions of circRNAs and discusses specific studies that provide insights into the function and potential of circRNAs for application in the diagnosis and treatment of kidney-related diseases.

Reciprocal Role Of DNA Methylation And Sp1 Binding In Ki-67 Gene Transcription.

PURPOSE: DNA methylation plays major regulatory roles in gene transcription. Our previous studies confirmed that Ki-67 promoter is hypomethylated and Sp1 is a transcriptional activator of Ki-67 gene in cancer cells. However, whether Sp1-mediated transcriptional activation of Ki-67 is related to its methylation has not been studied yet. MATERIALS AND METHODS: In this study, we confirmed that methylated CpG binding protein 2 (MBD2) binding to methylated DNA hindered the binding of Sp1 to Ki-67 promoter and then repressed Ki-67 transcription through chromatin immunoprecipitation (ChIP) and quantitative real-time PCR (qRT-PCR). Co-immunoprecipitation (Co-IP), ChIP, methylation-specific PCR (MS-PCR) and Western blot were utilized to analyze the effects of Sp1 binding to Ki-67 promoter on its methylation status. RESULTS: Less DNA methyltransferase 1 (DNMT1) bound to the Ki-67 promoter in MKN45 cells than in HK-2 cells. Histone acetyltransferase p300 that was recruited by Sp1 to Ki-67 promoter could attenuate the methylation level of Ki-67 promoter. Furthermore, higher expression of Sp1 and Ki-67 was related to the overall survival (OS), first progression (FP) and post-progression survival (PPS) in gastric cancer by scrutinizing bioinformatics datasets. CONCLUSION: Taken together, our findings suggested that hypomethylation of Ki-67 promoter enhanced the binding of Sp1, which in turn maintained hypomethylation of promoter, leading to increase Ki-67 expression in cancer cells. Sp1 and Ki-67 could act promising prognostic biomarkers for clinical diagnosis and treatment of cancer.

[ADRB2 Gene Knockout in Human Primary T Cells by Multiple sgRNAs Construced using CRISPR/Cas9 Technology].

OBJECTIVE: To knockout ADRB2 gene rapidly and efficiently in human primary T cells by using CRISPR/Cas9 technology and multiple sgRNAs strategy. METHODS: Six paired-sgRNAs, which were designed to target the 5' constitutive coding exons of ADRB2 gene, were cloned into pGL3-U6-sgRNA-PGK-Puro vector separately. The expre-ssion vectors containing the single sgRNAs were constructed and transiently co-transfected into HEK-293T cell line with Cas9 expression vector. The sgRNA-mediated cleavage efficiency was tested by T7EN I digestion assay. Concatenating four highly efficient paired sgRNAs were cloned into pGL3-U6-sgRNA-ccdB-EF1α-Puro expression vector. The reco-mbinant plasmid allows the cells to express 4 sgRNAs, which target different sites on the ADRB2 genomic locus. The cleavage efficiency and mutation model were tested by T7EN I digest assay and T-A cloning technique. Multiple sgRNAs plasmid and Cas9 plasmid was transiently transferred into human primary T cells by electroporation. Flow cytometry (FCM) was used to detect the knockout efficiency of ß2 adrenergic receptor (ß2-AR). RESULTS: The results of T7EN I digestion and TA cloning sequencing showed that the multiple sgRNAs strategy could obtain more abundant mutation types and higher gene editing efficiency than single sgRNA. In addition to the deletion and insertion of bases, large fragment DNA deletions and inversions could be observed. All of the random 10 TA clones for detection were genetically modified, thus the mutation efficiency was as high as 100%. FCM assay showed that 43.09% of the cells in the control T cells were ß2-AR positive, but the proportion of ß2-AR positive cells in the multiple sgRNAs electrotransformed T cells decreased to 25.61%. CONCLUSION: A method, which is simple and operable, for knocking out ß2-AR in human primary T cells has been established preliminarily. The results are helpful for the further study of the role of ß2-AR in human T cells.

Functional roles of circular RNAs during epithelial-to-mesenchymal transition.

Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMT-related circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.

Emerging Roles of p53 Related lncRNAs in Cancer Progression: A Systematic Review.

p53 is the major mediator of the tumor suppressor response. It participates in apoptosis and senescence and can respond to DNA damage. As a crucial sequence-specific transcription factor, p53 regulates the expression of many genes, such as small noncoding RNAs (ncRNAs), microRNAs, and long ncRNAs (lncRNAs). Given the emergence of novel and high-throughput sequencing technologies, many lncRNAs have been discovered. LncRNAs may function as vital gene regulators in a variety of biological processes through extensive mechanisms. Recently, lncRNAs have been demonstrated to be associated with the p53 regulatory pathway. In this review, we discuss the current and fast growing knowledge about the influence of lncRNAs to the p53 signaling pathway, the different mechanisms by which they affect gene expression in cancer. Our findings show that p53-associated lncRNAs may be used as biomarkers for cancer diagnosis or targets for disease therapy.

SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis.

Human homolog of mouse double minute 2 (HDM2) is an oncogene frequently overexpressed in cancers with poor prognosis, but mechanisms of controlling its abundance remain elusive. In an unbiased biochemical search, we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation. In human breast cancer cells, FBXO22 knockdown (KD) increased cell invasiveness, which was driven by elevated levels of HDM2. Moreover, mouse 4T1 breast tumor model studies revealed that FBXO22 KD led to a significant increase of breast tumor cell metastasis to the lung. Finally, low FBXO22 expression is correlated with worse survival and high HDM2 expression in human breast cancer. Altogether, these findings suggest that SCFFBXO22 targets HDM2 for degradation and possesses inhibitory effects against breast cancer tumor cell invasion and metastasis.

Relationship between expression of XRCC1 and tumor proliferation, migration, invasion, and angiogenesis in glioma.

Recently, XRCC1 polymorphisms were reported to be associated with glioma in Chinese population. However, only a few studies reported on the XRCC1 expression, and cancer progression. In this study, we investigated whether XRCC1 plays a role in glioma pathogenesis. Using the tissue microarray technology, we found that XRCC1 expression is significantly decreased in glioma compared with tumor adjacent normal brain tissue (P < 0.01, χ2 test) and reduced XRCC1 staining was associated with WHO stages (P < 0.05, χ2 test). The mRNA and protein levels of XRCC1 were significantly downregulated in human primary glioma tissues (P < 0.001, χ2 test). We also found that XRCC1 was significantly decreased in glioma cell lines compared to normal human astrocytes (P < 0.01, χ2 test). Overexpression of XRCC1 dramatically reduced the proliferation and caused cessation of cell cycle. The reduced cell proliferation is due to G1 phase arrest as cyclin D1 is diminished whereas p16 is upregulated. We further demonstrated that XRCC1 overexpression suppressed the glioma cell migration and invasion abilities by targeting MMP-2. In addition, we also found that overexpression of XRCC1 sharply inhibited angiogenesis, which correlated with down-regulation of VEGF. The data indicate that XRCC1 may be a tumor suppressor involved in the progression of glioma.

The roles of Wnt/ß-catenin signaling pathway related lncRNAs in cancer.

Long noncoding RNAs (lncRNAs), with length of more than 200 nucleotides, are not translated into proteins but involved in multiple diverse diseases, especially tumorigenesis. The dysregulation of lncRNAs greatly contributes to the progression of various tumors through specific signaling pathways, including Wnt/ß-catenin signaling pathway, which is associated with malignant features of tumors. The interactions between lncRNAs, which have specific expression characteristics in diverse cancer tissues, and Wnt/ß-catenin signaling pathway, exhibit potential as novel biomarkers and therapeutic targets. In this review, we aim to present research findings on the roles of Wnt pathway-related lncRNAs and their effects on Wnt/ß-catenin signaling to regulate tumorigenesis in different cancer types. Results may be used as basis to develop or improve strategies for treatment of different carcinomas.

CUL1 promotes breast cancer metastasis through regulating EZH2-induced the autocrine expression of the cytokines CXCL8 and IL11.

CUL1 is an essential component of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Our previous study has showed that CUL1 is positively associated with poor overall and disease-specific survival of breast cancer patients. Here, we further explored its roles in breast cancer metastasis. Our data showed that CUL1 significantly promoted breast cancer cell migration, invasion, tube formation in vitro, as well as angiogenesis and metastasis in vivo. In mechanism, the human gene expression profiling was used to determine global transcriptional changes in MDA-MB-231 cells, and we identified autocrine expression of the cytokines CXCL8 and IL11 as the target genes of CUL1 in breast cancer cell migration, invasion, metastasis, and angiogenesis. CUL1 regulated EZH2 expression to promote the production of cytokines, and finally significantly aggravating the breast cancer cell metastasis and angiogenesis through the PI3K-AKT-mTOR signaling pathway. Combined with the previous report about CUL1, we proposed that CUL1 may serve as a promising therapeutic target for breast cancer metastasis.

Suppression of Jab1 expression inhibits proliferation and promotes apoptosis of AMC-HN-8 cells.

c-Jun activation domain-binding protein-1 (Jab1) is a multifunctional protein involved in cell proliferation and apoptosis, DNA damage and repair and genome stability. In a number of types of human carcinoma, the abnormal expression of Jab1 is associated with poor prognosis, suggesting that Jab1 serves a vital function in tumorigenesis. However, the functional effects and the underlying molecular mechanisms of Jab1 in laryngeal squamous cell carcinoma (LSCC) progression remain poorly understood. The results of the present study demonstrate that downregulating Jab1 expression promotes LSCC apoptosis while inhibiting the proliferation of LSCC cells. Furthermore, Jab1 inhibition results in decreased protein kinase B phosphorylation accompanied by increased caspase-3 cleavage and p53 expression. It has been identified that the increased expression of Jab1 is markedly associated with LSCC progression, therefore Jab1 may be used as a novel target for the treatment of laryngeal cancer.

Inhibition of prostate cancer DU145 cell growth with small interfering RNA targeting the SATB1 gene.

Prostate cancer is a common visceral cancer of men worldwide. It is important to develop a more effective treatment for prostate cancer to overcome the treatment resistance that occurs with recurrence. RNA interference has been demonstrated to be a powerful tool for gene knockdown and has potential as a cancer treatment. It has been previously demonstrated that staining of special AT-rich sequence-binding protein 1 (SATB1) was stronger in prostatic carcinoma with metastasis compared with prostatic carcinoma without metastasis. In the present study, SATB1 small interfering (si)RNA was transfected into prostate cancer DU145 cells and normal human lung fibroblast cells, and cell proliferation was investigated using a Cell Counting kit-8. Three siRNA were transfected into cells using siPORT Lipid Transfection agent, and blank control and negative control groups were established. The cells were harvested and SATB1 mRNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. DU145 cell adhesion, migration and invasion capabilities were determined using cell adhesion, Transwell and Transwell with Matrigel assays, respectively. Silencing SATB1 significantly inhibited DU145 cell growth, adhesion, migration and invasive capability in vitro, indicating that a SATB1-targeting siRNA was successfully engineered. The results of the present study suggest that SATB1 siRNA may be a potential agent for treating human prostate cancer.

Lanatoside C inhibits cell proliferation and induces apoptosis through attenuating Wnt/ß-catenin/c-Myc signaling pathway in human gastric cancer cell.

Gastric cancer is the third common cause of cancer mortality in the world with poor prognosis and high recurrence due to lack of effective medicines. Our studies revealed that lanatoside C, a FDA-approved cardiac glycoside, had an anti-proliferation effect on different human cancer cell lines (MKN-45; SGC-7901; HN4; MCF-7; HepG2) and gastric cell lines MKN-45 and SGC-7901 were the most sensitive cell lines to lanatoside C. MKN-45 cells treated with lanatoside C showed cell cycle arrest at G2/M phase and inhibition of cell migration. Meanwhile, upregulation of cleaved caspase-9 and cleaved PARP and downregulation of Bcl-xl were accompanied with the loss of mitochondrial membrane potential (MMP) and induction of intracellular reactive oxygen species (ROS). Lanatoside C inhibited Wnt/ß-catenin signaling with downregulation of c-Myc, while overexpression of c-Myc reversed the anti-tumor effect of lanatoside C, confirming that c-Myc is a key drug target of lanatoside C. Furthermore, we discovered that lanatoside C prompted c-Myc degradation in proteasome-ubiquitin pathway with attenuating the binding of USP28 to c-Myc. These findings indicate that lanatoside C targeted c-Myc ubiquitination to inhibit MKN-45 proliferation and support the potential value of lanatoside C as a chemotherapeutic candidate.

Inhibition of prostate cancer cell growth in vivo with short hairpin RNA targeting SATB1.

Despite previous advances, the treatment options for prostate cancer remain limited. For the purposes of gene knockdown, the utility of RNA interference has been demonstrated and is considered to have therapeutic potential. In the present study, a short hairpin RNA (shRNA) was used to assess the effect of special AT-rich sequence binding protein (SATB1) downregulation on the growth and metastatic potential of prostate cancer in xenograft nude mice. A plasmid carrying shRNA targeting SATB1, pSilencer-SATB1-shRNA, was successfully engineered. Using this plasmid, significant downregulation of SATB1 mRNA and protein expression in the DU145 prostate cancer cells was observed. pSilencer-SATB1-shRNA was demonstrated to be markedly efficacious against prostate cancer xenografts in nude mice. These results may lead to a novel method of improving gene therapy efficacy against prostate cancer via regulating the function of SATB1.

Enhanced antiproliferative activity of antibody-functionalized polymeric nanoparticles for targeted delivery of anti-miR-21 to HER2 positive gastric cancer.

MiR-21 is an oncogenic miR frequently elevated in gastric cancer. Overexpression of miR-21 decreases the sensitivity of gastric cancer cells to trastuzumab, which is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2. However, optimization of miRNA or its anti-miRNA oligonucleotides (AMOs) for delivery is a challenge. Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including AMOs. This study is a continuation of our earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target gastric cancer cells with HER2 receptor over-expression using anti-miRNA-21 antisense oligonucleotides (AMO-21). The antibody conjugates (HER-PEG-PCL NPs) act against target cells via antibody-dependent mechanisms and also based on encapsutalated AMO-21. X-ray photoelectron spectroscopy validated the presence of trastuzumab on NP surface. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a stable antibody expression. The cell line specificity, cellular uptake, AMO-21 delivery, and cytotoxicity of the HER-PEG-PCL NPs were investigated. We found that the antibody conjugates significantly enhanced the cellular uptake of NPs. The HER-PEG-PCL NPs effectively suppressed the target miRNA expression in gastric cancer cells, which further up-regulated phosphatase and tensin homolog (PTEN). As a result, the sensitivity of HER2-expressing gastric cancer cells to trastuzumab was enhanced. The approach enhances the targeting by trastuzumab as well as antibody-dependent cellular cytotoxicity of immune effector cells. The antitumor effects of AMO-21-HER-PEG-PCL NPs were compared with trastuzumab in xenograft gastric cancer mice. The results provide insight into the biological and clinical potential of targeted AMO-21 delivery using modified trastuzumab for gastric cancer treatment.

The Role of Tumor Suppressor DLC-1: Far From Clear.

BACKGROUND: Deleted in liver cancer 1 (DLC-1) In human was originally isolated from rats brain and was often found to be deleted in hepatocellular carcinoma (HCC). METHODS: We undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. RESULTS: Subsequent studies have demonstrated that DLC-1 is generally expressed in normal human tissues as well as in rats, while it always exists inactivated or even lost in many human cancers, which characterizes DLC-1 as a potential tumor suppressor. Additionally, the RhoGAP (Rho-GTPase activating proteins) activity was found to play a pivotal role in regulating DLC-1. CONCLUSION: Although emerging studies in a variety of cancers have identified DLC-1 and its downstream signaling molecules as potential therapeutic targets for treatments of DLC-1-related cancers, the mechanisms linked to DLC-1 remain undefined.

HSP27 regulates TGF-ß mediated lung fibroblast differentiation through the Smad3 and ERK pathways.

Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease with unknown etiology. Recent studies have indicated that heat-shock protein 27 (HSP27) contributes to the pathogenesis of IPF through the regulation of epithelial-mesenchymal transition (EMT). However, the expression and role of HSP27 in fibroblasts during pulmonary fibrogenesis has not been investigated to date, at least to the best of our knowledge. In this study, we examined the expression of HSP27 in fibrotic lung tissue and fibroblasts from bleomycin (BLM)-challenged mice and human lung fibroblasts treated with transforming growth factor-ß (TGF-ß). The results revealed that the expression of HSP27 was significantly increased in fibrotic lung tissue and fibroblasts from BLM-challenged mice. In vitro, TGF-ß stimulated HSP27 expression in and the differentiation of human lung fibroblasts. The knockdown of Smad3 expression or nuclear factor-κB p65 subunit attenuated the TGF-ß-induced increase in HSP27 expression and the differentiation of human lung fibroblasts. In addition, the knockdown of HSP27 expression attenuated the TGF-ß-induced activation of ERK and Smad3, and inhibited the differentiation of human lung fibroblasts. On the whole, the findings of our study demonstrate that HSP27 expression is upregulated in lung fibroblasts during pulmonary fibrosis, and subsequently, HSP27 modulates lung fibroblast differentiation through the Smad3 and ERK pathways.

CTHRC1 mediates multiple pathways regulating cell invasion, migration and adhesion in glioma.

Recently, collagen triple helix repeat containing-1 (CTHRC1) has been reported to be increased in several types of human solid cancers and to be associated with tumor invasion and metastasis. However, the expression and function of CTHRC1 in glioma have not yet been reported. In the present study, we investigated whether CTHRC1 plays a role in glioma pathogenesis. Using the tissue microarray technology, we found that CTHRC1 expression is significantly increased in glioma compared with tumor adjacent normal brain tissue (P<0.01, χ2 test) and increased CTHRC1 staining was associated with WHO stages (P<0.05, χ2 test). The mRNA and protein levels of CTHRC1 were significantly upregulated in human primary glioma tissues (P<0.001, χ2 test). We also found that CTHRC1 was significantly increased in glioma cell lines compared to normal human astrocytes (P<0.01, χ2 test). Furthermore, Knockdown of CTHRC1 suppressed glioma cell invasion and inhibited enzyme activity of MMP-2. Moreover, our data showed that knockdown of CTHRC1 inhibited glioma cell migration and adhesion capacity when compared with the control cells, and CTHRC1-siRNA reduced the levels of phosphorylated Src and FAK protein expression. Taken together, this study suggests that CTHRC1 plays a role in glioma development and progression by regulating invasion, migration and adhesion capabilities of cancer cells.