MICAL2 Promotes Proliferation and Migration of Glioblastoma Cells Through TGF-β/p-Smad2/EMT-Like Signaling Pathway.
Ontology highlight
ABSTRACT:
SUBMITTER: Pu B
PROVIDER: S-EPMC8632809 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Previous studies revealed that Asporin (ASPN) is a potential mediator in the development of various types of cancer as a secreted stroma protein, but the function of ASPN inside the cancer cells remains largely unknown. Here, we demonstrated a higher expression level of ASPN in colorectal cancer (CRC) than matched normal tissues, and 25% (2/8) CRC showed copy number variation (CNV) gain/amplification in ASPN gene. Both higher ASPN expression levels and ASPN CNV gain/amplification indicated a worse prognosis in CRC patients. ASPN can promote proliferation, migration, and invasion of CRC cells, and inhibit apoptosis by activating Akt/Erk and TGF-β/Smad2/3 signalings. Further investigations revealed that ASPN interacts with Smad2/3, facilitates its translocation into nucleus, and up-regulates the expression of Epithelial-mesenchymal transition (EMT) related genes. Rescue assays confirmed that TGF-β signaling is essential for the effects of ASPN on promoting CRC cell migration and invasion. In conclusion, ASPN promotes the migration and invasion of CRC cells via TGF-β/Smad2/3 pathway and could serve as a potential prognostic biomarker in CRC patients.
| S-EPMC6365561 | biostudies-literature
Project description:Eukaryotic translation elongation factor 1δ (EEF1D), a subunit of the elongation factor 1 complex of proteins, mediates the elongation process of protein synthesis. Besides this canonical role, EEF1D was found overexpressed in many tumors, like hepatocarcinomas and medulloblastomas. In the present study, we demonstrated for the first time that EEF1D may interact with other putative proteins to regulate cell proliferation, migration, and invasion through PI3K/Akt and EMT pathways in glioma. Furthermore, knockdown of EEF1D could reduce cell proliferation and impaired epithelial-mesenchymal transition (EMT) phenotypes, including cell invasion. Taken together, these results indicate that EEF1D and its partner proteins might play a critical role in glioma and serve as a potential therapeutic target of glioma.
| S-EPMC7533006 | biostudies-literature
Project description:ObjectiveSmall cell lung carcinoma (SCLC) is considered one of the most aggressive types of lung cancer due to its rapid growth and early metastasis. No tumor markers or therapeutic targets have been demonstrated to be specific or effective in SCLC to date. This study aims to evaluate the potential of Flotillin1 (Flot1) as a target of SCLC treatment.MethodsFlot1 expression level in the tissue of SCLC and other tissue of lung disease was detected using immunohistochemical staining. Transwell and Matrigel assays were employed to examine migration and invasion of cancer cells. Flow cytometry and xCELLigence system were used to evaluate cell apoptosis and cell viability, respectively. Expression levels of Flot1, epithelial-mesenchymal transition (EMT) marker E-cadherin, vimentin, cyclinD1, TGF-β-Smad2/3, and p-AKT were examined using Western blot. Furthermore, xenograft tumor in nude mice was used to evaluate the growth and metastasis of NCI-H446 cells in vivo.ResultsOur results demonstrated that Flot1 is highly expressed in SCLC samples and that its expression correlates strongly with clinical stage, distant metastasis, and poor survival. The knockdown of Flot1 decreased the growth, migration, and invasiveness of SCLC cells and reversed EMT phenotype in vitro and in vivo, while enhanced Flot1 expression exhibited the opposite behavior. Gene expression profile analysis demonstrated that Flot1-regulated genes frequently mapped to the AKT and TGF-β-Smad2/3 pathways. Our results further revealed that Flot1 affected the progression of SCLC via regulation of EMT progression.ConclusionsThese findings indicated an oncogenic role of Flot1 via promoting EMT in SCLC and suggested its potential as a tumor marker and prognostic indicator.
| S-EPMC6372910 | biostudies-literature
Project description:HoxB9, as a HOX family member, is known to play important roles in embryonic development. Recent studies have shown that HoxB9 is involved in cancer progression. However, little is known about the role of HoxB9 and the underlying mechanisms that suppress oral squamous cell carcinoma (OSCC) progression. In the present study, we used immunohistochemical staining to demonstrate that HoxB9 is over-expressed in OSCC cells and found that high levels of HoxB9 were significantly associated with shorter overall survival in patients with OSCC. Functional studies revealed that knocking down HoxB9 in OSCC cells using RNA interference decreased the migration and invasion of OSCC cells in vitro. Our mechanistic studies suggested that HoxB9 could stimulate the migration and invasion of OSCC cells by targeting EMT via the TGF-β1/Smad2/Slug signaling pathway. Collectively, these findings suggest the vital roles of HoxB9 in OSCC progression through its effects in promoting EMT.
| S-EPMC5376006 | biostudies-literature
Project description:In this study, we analyzed GPC family genes in colorectal cancer (CRC) and the possible mechanism of action of GPC1 in CRC. CRC patient data were extracted from The Cancer Genome Atlas, and the prognostic significance of GPC1 expression and its association with clinicopathological features were identified by Kolmogorov-Smirnov test. CRC patients with high GPC1 expression had poor overall survival compared with patients with low GPC1 expression. In vitro experiments demonstrated that knockdown of GPC1 significantly inhibited the proliferation and migration and promoted cell apoptosis in CRC cell lines. Gene Ontology analysis of differential genes indicated that GPC1 may influence the TGF-β1 signaling pathway. Additional experiments revealed that silencing GPC1 suppressed the levels of TGF-β1 and p-SMAD2 but increased the expression of SMAD2. Taken together, these findings suggest that GPC1 may function as a tumor promoter in CRC cells through promoting TGF-β signaling pathway. Our results also indicate that GPC1 may serve as a critical effector in CRC progression and a new potential target for CRC therapy.
| S-EPMC9173621 | biostudies-literature
Project description:IntroductionMicrofibril-associated protein 2 (MFAP2) is an extracellular matrix protein that interacts with fibrillin to modulate the function of microfibrils. MFAP2 has been reported to play a significant role in obesity, diabetes, and osteopenia, and has been shown to be upregulated in head and neck squamous cell carcinoma. However, the molecular function and prognostic value of MFAP2 have never been reported in gastric cancer (GC) or any other tumors.MethodsThe current study investigated the expression patterns, prognostic significance, functional role, and possible mechanisms of MFAP2 in GC.ResultsWe demonstrated that MFAP2 was overexpressed in GC tissues, and its overexpression was significantly correlated with poor overall and disease-free survival in patients with GC. Moreover, we found that MFAP2 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) phenotype in GC cells. MFAP2 might modulate EMT of GC cells by activating the TGF-β/SMAD2/3 signaling pathway.ConclusionThese findings provide novel evidence that MFAP2 plays a crucial role in the progression of GC. Therefore, MFAP2 may be a promising prognostic marker and a potent anticancer agent.
| S-EPMC6047603 | biostudies-literature
Project description:AbstrictLINC00941 is a novel lncRNA that has been found to exhibit protumorigenic and prometastatic behaviors during tumorigenesis. However, its role in metastatic CRC remains unknown. We aimed to investigate the functions and mechanisms of LINC00941 in CRC metastasis. LINC00941 was shown to be upregulated in CRC, and upregulated LINC00941 was associated with poor prognosis. Functionally, LINC00941 promoted migratory and invasive capacities and accelerated lung metastasis in nude mice. Mechanistically, LINC00941 activated EMT in CRC cells, as indicated by the increased expression of key molecular markers of cell invasion and metastasis (Vimentin, Fibronectin, and Twist1) and simultaneous decreased expression of the main invasion suppressors E-cadherin and ZO-1. LINC00941 was found to activate EMT by directly binding the SMAD4 protein MH2 domain and competing with β-TrCP to prevent SMAD4 protein degradation, thus activating the TGF-β/SMAD2/3 signaling pathway. Our data reveal the essential role of LINC00941 in metastatic CRC via activation of the TGF-β/SMAD2/3 axis, which provides new insight into the mechanism of metastatic CRC and a novel potential therapeutic target for advanced CRC.
| S-EPMC7853066 | biostudies-literature
Project description:Glioblastoma (GBM) is the most prevalent primary malignancy of the central nervous system with obvious aggressiveness, and is associated with poor clinical outcome. Studies have indicated that calcium ion (Ca2+ ) can positively regulate the initiation of malignancy with regard to GBM by modulating quiescence, proliferation, migration and maintenance. Hippocalcin like-1 protein (HPCAL1) serves as a sensor of Ca2+ . However, the understanding of HPCAL1 activity in GBM is limited. The present study revealed that the gene HPCAL1 was up-regulated by Ca2+ in the tissues and cells of GBM. Ectopic expression of HPCAL1 promoted proliferation of cells. Exhaustion of HPCAL1 inhibited cell growth not only in vivo, but also in vitro. In addition, HPCAL1 enhanced the Wnt pathway by stimulating β-catenin accumulation and nuclear translocation in GBM cells, while β-catenin silencing significantly inhibited the proliferation and growth of the GBM cells. Our results showed that Ser9 phosphorylation of GSK3β was significantly decreased after HPCAL1 knockdown in GBM cells, and knockdown of the gene GSK3β in GBM cells enhanced cell proliferation and promoted transcription of the genes CCND1 and c-Myc. Furthermore, the phosphorylation of ERK was decreased in the cells with HPCAL1 knockdown, while it was promoted via overexpression of HPCAL1. The suppression or depletion of the gene ERK decreased proliferation triggered by overexpression of HPCAL1 and impaired transcription of the genes c-Myc and CCND1. These studies elucidate the tumour-promoting activity of HPCAL1. They also offer an innovative therapeutic strategy focusing on the HPCAL1-Wnt/β-catenin axis to regulate proliferation and development of GBM.
| S-EPMC6484330 | biostudies-literature
Project description:Glioblastoma (GBM) is a primary malignant tumor characterized by high infiltration and angiogenesis in the brain parenchyma. Glioma stem cells (GSCs), a heterogeneous GBM cell type with the potential for self-renewal and differentiation to tumor cells, are responsible for the high malignancy of GBM. The purpose of the present study was to investigate the roles of significantly differentially expressed genes between GSCs and GBM cells in GBM progression. The gene profiles GSE74304 and GSE124145, containing 10 GSC samples and 12 GBM samples in total, were obtained from the Gene Expression Omnibus (GEO) database. The overlapping differentially expressed genes were identified with GEO2R tools and Venn software online. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed on the 41 upregulated and 142 downregulated differentially expressed genes in GSCs compared with in GBM cells via the DAVID website. Protein-protein interaction and module analyses in Cytoscape with the STRING database revealed 21 hub genes that were downregulated in GSCs compared with in GBM cells. Survival analysis conducted via the GEPIA2 website revealed that low expression levels of the hub genes prolyl 4-hydroxylase subunit α2 (P4HA2), TGF-β induced, integrin subunit α3 and thrombospondin 1 were associated with significantly prolonged survival time in patients with GBM. Further experiments were performed focusing on P4HA2. Reverse transcription-quantitative PCR was used to detect P4HA2 gene expression. In agreement with the bioinformatics analysis, P4HA2 expression was higher in U87 cells than in GSCs. Cell Counting Kit-8, EdU incorporation, cell cycle analysis, wound healing and Transwell assays demonstrated that the cell proliferation and migration increased after P4HA2 overexpression and decreased after P4HA2-knockdown. In conclusion, the present study demonstrated that low P4HA2 expression in GSCs promoted GBM cell proliferation and migration, suggesting that P4HA2 may act as a switch in the transition from GSCs to GBM cells.
| S-EPMC8228437 | biostudies-literature
Project description:Glioblastoma (GBM) generally has a dismal prognosis, and it is associated with a poor quality of life as the disease progresses. However, the development of effective therapies for GBM has been deficient. Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family in the ubiquitin-proteasome pathway and a vital regulator of tumour progression, but its role in GBM is unclear. In this study, we aimed to clarify the role of UBE2T in GBM. Bioinformatics analysis identified UBE2T as an independent risk factor for gliomas. Immunohistochemistry was used to measure UBE2T expression in GBM and normal tissue samples obtained from patients with GBM. The effects of UBE2T on GBM cell invasion and migration were analysed using the Transwell assay. BALB/c nude mice were used for the in vivo assays. Immunoblotting and immunoprecipitation were performed to determine the molecular mechanisms. UBE2T was highly expressed in GBM tissues, and its expression was linked to a poor prognosis. In vitro, depletion of UBE2T significantly suppressed cell invasion and migration. Moreover, UBE2T depletion suppressed the growth of GBM subcutaneous tumours in vivo. Further experiments revealed that UBE2T suppressed invasion and migration by regulating epithelial- mesenchymal transition (EMT) via stabilising GRP78 in GBM cells. We uncovered a novel UBE2T/GRP78/EMT regulatory axis that modulates the malignant progression and recurrence of GBM, indicating that the axis might be a valuable therapeutic target.
| S-EPMC7346020 | biostudies-literature