scholarly journals CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion

2019 ◽  
Vol 20 (5) ◽  
pp. 1137 ◽  
Author(s):  
Lais Cardoso ◽  
Roseli Soares ◽  
Talita Laurentino ◽  
Antonio Lerario ◽  
Suely Marie ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Molecular Subtypes ◽  
Transmembrane Protein ◽  
Standard Of Care ◽  
Actin Dynamics ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Current Standard ◽  
Tumor Cell Migration

Glioblastoma (GBM) is the most aggressive type of brain tumor, with an overall survival of 17 months under the current standard of care therapy. CD99, an over-expressed transmembrane protein in several malignancies, has been considered a potential target for immunotherapy. To further understand this potentiality, we analyzed the differential expression of its two isoforms in human astrocytoma specimens, and the CD99 involved signaling pathways in glioma model U87MG cell line. CD99 was also analyzed in GBM molecular subtypes. Whole transcriptomes by RNA-Seq of CD99-siRNA, and functional in vitro assays in CD99-shRNA, that are found in U87MG cells, were performed. Astrocytoma of different malignant grades and U87MG cells only expressed CD99 isoform 1, which was higher in mesenchymal and classical than in proneural GBM subtypes. Genes related to actin dynamics, predominantly to focal adhesion, and lamellipodia/filopodia formation were down-regulated in the transcriptome analysis, when CD99 was silenced. A decrease in tumor cell migration/invasion, and dysfunction of focal adhesion, were observed in functional assays. In addition, a striking morphological change was detected in CD99-silenced U87MG cells, further corroborating CD99 involvement in actin cytoskeleton rearrangement. Inhibiting the overexpressed CD99 may improve resectability and decrease the recurrence rate of GBM by decreasing tumor cells migration and invasion.

scholarly journals Integrin α9 Suppresses Hepatocellular Carcinoma Metastasis by Rho GTPase Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yan-Li Zhang ◽  
Xin Xing ◽  
Li-Bo Cai ◽  
Lei Zhu ◽  
Xiao-Mei Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Focal Adhesion ◽  
Molecular Mechanisms ◽  
Rho Gtpase ◽  
Migration And Invasion ◽  
Integrin Subunit ◽  
Src Tyrosine Kinase ◽  
Tumor Cell Migration

Integrin subunit alpha 9 (ITGA9) mediates cell-cell and cell-matrix adhesion, cell migration, and invasion through binding different kinds of extracellular matrix (ECM) components. However, its potential role and underlying molecular mechanisms remain unclear in hepatocellular carcinoma (HCC). Here, we found that ITGA9 expression was obviously decreased in patients with HCC, which was negatively correlated with HCC growth and metastasis. ITGA9 overexpression significantly inhibited cell proliferation and migration in vitro as well as tumor growth and metastasis in vivo. Our data demonstrated that the inhibitory effect of ITGA9 on HCC cell motility was associated with reduced phosphorylation of focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src), disrupted focal adhesion reorganization, and decreased Rac1 and RhoA activity. Our data suggest ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness through FAK/Src-Rac1/RhoA signaling.

Phosphorylated Caveolin-1 Regulates Rho/ROCK-Dependent Focal Adhesion Dynamics and Tumor Cell Migration and Invasion

2008 ◽  
Vol 68 (20) ◽  
pp. 8210-8220 ◽  
Author(s):  
Bharat Joshi ◽  
Scott S. Strugnell ◽  
Jacky G. Goetz ◽  
Liliana D. Kojic ◽  
Michael E. Cox ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Focal Adhesion ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tumor Cell Migration ◽  
Caveolin 1

scholarly journals LncRNA GHET1 Promotes Esophageal Squamous Cell Carcinoma Cells Proliferation and Invasion via Induction of EMT

2017 ◽  
Vol 32 (4) ◽  
pp. 403-408 ◽  
Author(s):  
Hongfen Liu ◽  
Qiang Zhen ◽  
Yakun Fan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Advanced Tumor

Background Recent studies have shown that long noncoding RNA (IncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) was involved in the progression of tumors. However, the role of GHET1 in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods The expression of IncRNA GHET1 was examined in 55 paired ESCC tissues and adjacent nontumor tissues. Molecular and cellular techniques were used to explore the role of GHET1 on ESCC cells. Results Our data showed that GHET1 expression was significantly increased in ESCC tissues and cell lines. High GHET1 expression in ESCC tissues was significantly associated with poor differentiation, advanced tumor nodes metastasis stage, and lymph node metastasis. GHET1 showed high sensitivity and specificity for diagnosing ESCC. Our data from in vitro assays showed that GHET1 inhibition suppressed ESCC cells proliferation, migration, and invasion, and induced cells apoptosis. Furthermore, western blot showed that GHET1 inhibition significantly decreased the expression of vimentin and N-cadherin while it increased the expression of E-cadherin. Conclusions Our study indicates that GHET1 acts as an oncogene in ESCC and may represent a novel therapeutic target for the treatment of ESCC patients.

scholarly journals Single-cell analysis revealed that IL4I1 promoted ovarian cancer progression

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongyu Zhao ◽  
Yu Teng ◽  
Wende Hao ◽  
Jie Li ◽  
Zhefeng Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Cell ◽  
Cancer Progression ◽  
Cox Regression ◽  
Single Cell Analysis ◽  
Cell Types ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Dominant Type

Abstract Background Ovarian cancer was one of the leading causes of female deaths. Patients with OC were essentially incurable and portends a poor prognosis, presumably because of profound genetic heterogeneity limiting reproducible prognostic classifications. Methods We comprehensively analyzed an ovarian cancer single-cell RNA sequencing dataset, GSE118828, and identified nine major cell types. Relationship between the clusters was explored with CellPhoneDB. A malignant epithelial cluster was confirmed using pseudotime analysis, CNV and GSVA. Furthermore, we constructed the prediction model (i.e., RiskScore) consisted of 10 prognosis-specific genes from 2397 malignant epithelial genes using the LASSO Cox regression algorithm based on public datasets. Then, the prognostic value of Riskscore was assessed with Kaplan–Meier survival analysis and time-dependent ROC curves. At last, a series of in-vitro assays were conducted to explore the roles of IL4I1, an important gene in Riskscore, in OC progression. Results We found that macrophages possessed the most interaction pairs with other clusters, and M2-like TAMs were the dominant type of macrophages. C0 was identified as the malignant epithelial cluster. Patients with a lower RiskScore had a greater OS (log-rank P < 0.01). In training set, the AUC of RiskScore was 0.666, 0.743 and 0.809 in 1-year, 3-year and 5-year survival, respectively. This was also validated in another two cohorts. Moreover, downregulation of IL4I1 inhibited OC cells proliferation, migration and invasion. Conclusions Our work provide novel insights into our understanding of the heterogeneity among OCs, and would help elucidate the biology of OC and provide clinical guidance in prognosis for OC patients.

scholarly journals Antitumor Activity of Nanoparticles Loaded with PHT-427, a Novel AKT/PDK1 Inhibitor, for the Treatment of Head and Neck Squamous Cell Carcinoma

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1242
Author(s):  
Joaquín Yanes-Díaz ◽  
Raquel Palao-Suay ◽  
María Rosa Aguilar ◽  
Juan Ignacio Riestra-Ayora ◽  
Antonio Ferruelo-Alonso ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Polymeric Nanoparticles ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Neck Squamous Cell Carcinoma ◽  
Current Standard

Currently, new treatments are required to supplement the current standard of care for head and neck squamous cell carcinoma (HNSCC). The phosphatidylinositol3-kinase (PI3K) signaling pathway is commonly altered and activated in HNSCC. PHT-427 is a dual PI3K-mammalian target of the AKT/PDK1 inhibitor; however, to the best of our knowledge, the effect of the PHT-427 inhibitor on HNSCC has not been investigated. This study aims to evaluate the antitumoral effect of PHT-427-loaded polymeric nanoparticles based on α-tocopheryl succinate (α-TOS). The in vitro activity of PHT-427 was tested in hypopharynx carcinoma squamous cells (FaDu) to measure the cell viability, PI3KCA/AKT/PDK1 gene expression, and PI3KCA/AKT/PDK1 levels. Apoptosis, epidermal growth factor receptor (EGFR), and reactive oxygen species (ROS) were also measured. The presence of PHT-427 significantly enhances its antiproliferative and proapoptotic activity by inactivating the PI3K/AKT/PDK1 pathway. Nanoparticles (NPs) effectively suppress AKT/PDK1 expression. Additionally, NPs loaded with PHT-427 produce high oxidative stress levels that induce apoptosis. In conclusion, these results are promising in the use of this nanoformulation as a PHT-427 delivery system for effective HNSCC treatment.

scholarly journals Rab40/Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration and invasion

2021 ◽  
Author(s):  
Erik S Linklater ◽  
Emily Duncan ◽  
Ke Jun Han ◽  
Algirdas Kaupinis ◽  
Mindaugas Valius ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Stress Fibers ◽  
Actin Dynamics ◽  
Migration And Invasion ◽  
Matrix Remodeling ◽  
Cell Migration And Invasion

Rab40b is a SOCS box containing protein that regulates the secretion of MMPs to facilitate extracellular matrix remodeling during cell migration. Here we show that Rab40b interacts with Cullin5 via the Rab40b SOCS domain. We demonstrate that loss of Rab40b/Cullin5 binding decreases cell motility and invasive potential, and show that defective cell migration and invasion stem from alteration to the actin cytoskeleton, leading to decreased invadopodia formation, decreased actin dynamics at the leading edge, and an increase in stress fibers. We also show that these stress fibers anchor at less dynamic, more stable focal adhesions. Mechanistically, changes in the cytoskeleton and focal adhesion dynamics are mediated in part by EPLIN, which we demonstrate to be a binding partner of Rab40b and a target for Rab40b/Cullin5 dependent localized ubiquitylation and degradation. Thus, we propose a model where the Rab40b/Cullin5 dependent ubiquitylation regulates EPLIN localization to promote cell migration and invasion by altering focal adhesion and cytoskeletal dynamics.

scholarly journals Antioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vanilla Xin Zhang ◽  
Karen Man-Fong Sze ◽  
Lo-Kong Chan ◽  
Daniel Wai-Hung Ho ◽  
Yu-Man Tsui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatoma Cell ◽  
Tumor Formation ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Intracellular Ros ◽  
Antioxidant Supplements ◽  
Sphere Formation

Abstract Background Controversy over the benefits of antioxidants supplements in cancers persists for long. Using hepatocellular carcinoma (HCC) as a model, we investigated the effects of exogenous antioxidants N-acetylcysteine (NAC) and glutathione (GSH) on tumor formation and growth. Methods Multiple mouse models, including diethylnitrosamine (DEN)-induced and Trp53KO/C-MycOE-induced HCC models, mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection were used. In vitro assays including ROS assay, colony formation, sphere formation, proliferation, migration and invasion, apoptosis, cell cycle assays were conducted. Western blot was performed for protein expression and RNA-sequencing to identify potential gene targets. Results In these multiple different mouse and cell line models, we observed that NAC and GSH promoted HCC tumor formation and growth, accompanied with significant reduction of intracellular reactive oxygen species (ROS) levels. Moreover, NAC and GSH promoted cancer stemness, and abrogated the tumor-suppressive effects of Sorafenib both in vitro and in vivo. Exogenous supplementation of NAC or GSH reduced the expression of NRF2 and GCLC, suggesting the NRF2/GCLC-related antioxidant production pathway might be desensitized. Using transcriptomic analysis to identify potential gene targets, we found that TMBIM1 was significantly upregulated upon NAC and GSH treatment. Both TCGA and in-house RNA-sequence databases showed that TMBIM1 was overexpressed in HCC tumors. Stable knockdown of TMBIM1 increased the intracellular ROS; it also abolished the promoting effects of the antioxidants in HCC cells. On the other hand, BSO and SSA, inhibitors targeting NAC and GSH metabolism respectively, partially abrogated the pro-oncogenic effects induced by NAC and GSH in vitro and in vivo. Conclusions Our data implicate that exogenous antioxidants NAC and GSH, by reducing the intracellular ROS levels and inducing TMBIM expression, promoted HCC formation and tumor growth, and counteracted the therapeutic effect of Sorafenib. Our study provides scientific insight regarding the use of exogenous antioxidant supplements in cancers.

Novel Neonatal Umbilical Catheter Protection and Stabilization Device in In vitro Model of Catheterized Human Umbilical Cords: Effect of Material and Venting on Bacterial Colonization

2019 ◽  
Author(s):  
Lauren S. Y. Wood ◽  
Janene H. Fuerch ◽  
Carl L. Dambkowski ◽  
Eric F. Chehab ◽  
Shivani Torres ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Bacterial Load ◽  
Standard Of Care ◽  
Adhesive Tape ◽  
Human Umbilical Cord ◽  
Current Standard ◽  
Central Lines ◽  
Umbilical Cords

Abstract Objective Umbilical central lines deliver life-saving medications and nutrition for neonates; however, complications associated with umbilical catheters (UCs) occur more frequently than in adults with central lines (i.e., line migration, systemic infection). We have developed a device for neonatal UC protection and stabilization to reduce catheter exposure to bacteria compared with the standard of care: “goal post” tape configuration. This study analyzes the effect of device venting and material on bacterial load of human umbilical cords in vitro. Study Design Catheters were inserted into human umbilical cord segments in vitro, secured with plastic or silicone vented prototype versus tape, and levels of bacterial colonization were compared between groups after 7 days of incubation. Results Nonvented plastic prototype showed increased bacterial load compared with goal post (p = 0.04). Colonization was comparable between the goal post and all vented plastic prototypes (p ≥ 0.30) and when compared with the vented silicone device (p = 1). Conclusion A novel silicone device does not increase external bacterial colonization compared with the current standard of care for line securement, and may provide a safe, convenient alternative to standard adhesive tape for UC stabilization. Future studies are anticipated to establish safety in vivo, alongside benefits such as migration and infection reduction.

scholarly journals CircATRNL1 promotes epithelial–mesenchymal transition in endometriosis by upregulating Yes-associated protein 1 in vitro

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Dandan Wang ◽  
Yajuan Luo ◽  
Guangwei Wang ◽  
Qing Yang
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Quantitative Polymerase Chain Reaction ◽  
Polymerase Chain Reaction Analysis ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Inhibitory Function ◽  
Ishikawa Cells

Abstract Endometriosis is a common and benign gynecological disorder but exhibits malignant features. However, the underlying pathogenesis and pathophysiology of endometriosis remain unclear. Circular RNAs have been demonstrated to participate in the occurrence and progression of multiple diseases. This study was aimed to explore the roles of circATRNL1 in endometriosis in vitro. Based on the results of reverse transcription-quantitative polymerase chain reaction analysis, we found significant upregulation of circATRNL1 and Yes-associated protein 1 (YAP1), while downregulation of miR-141-3p and miR-200a-3p in ectopic tissues compared to eutopic tissues. The immunohistochemistry and western blot analysis showed differentially expressed epithelial–mesenchymal transition (EMT) markers between EuEM and EcEM tissues. The in vitro assays indicated that overexpression of circATRNL1 could promote the proliferation, migration, and invasion of Ishikawa cells, and induce EMT process, while circATRNL1 silencing showed the opposite effect. The mechanical investigation indicated that circATRNL1 upregulated YAP1 by sponging miR-141-3p and miR-200a-3p. Gain-of-function assays validated the inhibitory function of miR-141-3p and miR-200a-3p in endometriosis. The results of rescue assays confirmed the function of circATRNL1–miR-141-3p/miR-200a-3p–YAP1 axis on Ishikawa cells. Our findings demonstrate that abnormal upregulation of circATRNL1 regulates cell proliferation and motility and promotes EMT process via the miR-141-3p/miR-200a-3p–YAP1 axis in vitro, which could contribute to the progression of endometriosis.

scholarly journals Antitumor Activity of Curcumin in Glioblastoma

2020 ◽  
Vol 21 (24) ◽  
pp. 9435
Author(s):  
Blake C. Walker ◽  
Sandeep Mittal
Keyword(s):  
Curcuma Longa ◽  
Malignant Gliomas ◽  
Standard Of Care ◽  
Additional Treatment ◽  
Treatment Modalities ◽  
Molecular Signaling ◽  
Current Standard ◽  
Traditional Medicines ◽  
Tumor Treating Fields

Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune® therapy, Novocure Ltd., Haifa, Israel), survival can be extended up to 20 months. In spite of significant progress in our understanding of the molecular pathogenesis, the prognosis for patients with malignant gliomas remains poor and additional treatment modalities are critically needed. Curcumin is a bright yellow pigment found in the rhizome of the widely utilized spice, turmeric (Curcuma longa). It has long been used in South Asian traditional medicines and has been demonstrated to have in vitro antioxidant, anti-inflammatory, and antiproliferative effects. Curcumin has been demonstrated to induce multiple cytotoxic effects in tumor cells including cell cycle arrest, apoptosis, autophagy, changes in gene expression, and disruption of molecular signaling. Additionally, curcumin has been shown to potentiate the effect of radiation on cancer cells, while exhibiting a protective effect on normal tissue. Curcumin’s positive safety profile and widespread availability make it a promising compound for future clinical trials for high-grade gliomas.

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