A Multi-targeted Natural Flavonoid Myricetin Suppresses Lamellipodia and Focal Adhesions Formation and Impedes Glioblastoma Cell Invasiveness and Abnormal Motility

2018 ◽  
Vol 17 (7) ◽  
pp. 557-567 ◽  
Author(s):  
Hua-Fu Zhao ◽  
Gang Wang ◽  
Chang-Peng Wu ◽  
Xiu-Ming Zhou ◽  
Jing Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Vasculogenic Mimicry ◽  
Focal Adhesions ◽  
Inhibitory Effect ◽  
Primary Brain Tumor ◽  
Brain Parenchyma ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Anti Oxidant ◽  
Cell Invasiveness

Background: Glioblastoma multiforme (GBM) is the most aggressive and malignant primary brain tumor characterized by rapid growth and extensive infiltration to neighboring normal brain parenchyma, which contribute to tumor recurrence and poor prognosis. Myricetin is a natural flavonoid with potent anti-oxidant, anti-inflammatory and anti-cancer activities, which may serve as a potential and harmless agent for GBM treatment. Methods: To investigate the anti-glioblastoma effects of myricetin, GBM cells were treated with myricetin alone or in combination with temozolomide. Its effects on GBM cell motility and cytoskeletal structures including lamellipodia, focal adhesions and membrane ruffles were also evaluated. Results: We showed that myricetin alone inhibited glioblastoma U-87 MG cell proliferation, migration and invasion, whereas combination of myricetin and temozolomide did not exhibit any synergistic effect. The inhibitory effect on GBM cell proliferation is independent of PTEN status. Moreover, myricetin showed less cytotoxicity to normal astrocytes than GBM cells. Formation of lamellipodia, focal adhesions, membrane ruffles and vasculogenic mimicry were blocked by myricetin, and phosphorylation of ROCK2, paxillin and cortactin was suppressed. In addition, myricetin could inhibit PI3K/Akt and JNK signaling, and bind to a series of kinases and scaffold proteins including PI3K catalytic isoforms (p110α, p110β and p110δ), PDK1, JNK, c-Jun, ROCK2, paxillin, vinculin and VEcadherin. Conclusions: In conclusion, myricetin is a multi-targeted drug that has potent anti-migratory and antiinvasive effects on GBM cells, and suppresses formation of lamellipodia and focal adhesions, suggesting that it may serve as an alternative option for GBM treatment.

scholarly journals MCP-1 and MIP-3α Secreted from Necrotic Cell-Treated Glioblastoma Cells Promote Migration/Infiltration of Microglia

2018 ◽  
Vol 48 (3) ◽  
pp. 1332-1346 ◽  
Author(s):  
Yieun Jung ◽  
So-Hee Ahn ◽  
Hyunju Park ◽  
Sang Hui Park ◽  
Kyungsun Choi ◽  
...  
Keyword(s):  
Protein Expression ◽  
Primary Brain Tumor ◽  
Brain Parenchyma ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Glioblastoma Cells ◽  
Mobility Shift ◽  
Diffuse Infiltration ◽  
Nuclear Extracts ◽  
Mrna And Protein Expression

Background/Aims: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The defining characteristics of GBM are diffuse infiltration of tumor cells into normal brain parenchyma, rapid growth, a high degree of infiltration of microglia and macrophages, and the presence of necrosis. Microglia/macrophages are frequently found in gliomas and they extensively infiltrate GBM tissue, up to 30% of total tumor mass. However, little is known about the effect of necrotic cells (NCs) on microglia infiltration in GBM and the tumor-infiltrating microglia-induced factors in GBMs. Methods: In this study, to address whether necrosis or necrosis-exposed GBM cells affect the degree of microglia/macrophage infiltration, migration and invasion/infiltration assays were performed. Culture supernatants and nuclear extracts of CRT-MG cells treated or untreated with necrotic cells were analyzed using a chemokine array and electrophoretic mobility shift assay, respectively. Results: The presence of NCs promoted the migration/infiltration of microglia, and GBM cell line CRT-MG cells exposed to NCs further enhanced the migration and infiltration of HMO6 microglial cells. Treatment with NCs induced mRNA and protein expression of chemokines such as <unterline>M</unterline>onocyte <unterline>C</unterline>hemoattractant <unterline>P</unterline>rotein-1 (CCL2/MCP-1) and <unterline>M</unterline>acrophage <unterline>I</unterline>nflammatory <unterline>P</unterline>rotein-3α (CCL20/MIP-3α) in CRT-MG cells. In particular, CCL2/MCP-1 and CCL20/MIP-3α were significantly increased in NC-treated CRT-MG cells. NCs induced DNA binding of the transcription factors <unterline>N</unterline>uclear <unterline>F</unterline>actor (NF)-κB and <unterline>A</unterline>ctivator <unterline>P</unterline>rotein 1 (AP-1) to the CCL2/MCP-1 and CCL20/MIP-3α promoters, leading to increased CCL2/MCP-1 and CCL20/MIP-3α mRNA and protein expression in CRT-MG cells. Conclusion: These results provide evidence that NCs induce the expression of CCL2/MCP-1 and CCL20/MIP-3α in glioblastoma cells through activation of NF-κB and AP-1 and facilitate the infiltration of microglia into tumor tissues.

FOXD3 inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma through regulation of the PI3K–Akt pathway

2020 ◽  
Vol 98 (6) ◽  
pp. 653-660 ◽  
Author(s):  
Xiaoxing Xie ◽  
Gaoyun Xiong ◽  
Wenjun Chen ◽  
Hongdan Fu ◽  
Mingqian Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Apoptosis ◽  
Inhibitory Effect ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Protein Levels ◽  
Flow Cytometric ◽  
Phosphoinositide 3 Kinase

FOXD3 has been found previously to positively regulate miR-26b, a tumor inhibitor of nasopharyngeal carcinoma (NPC). However, FOXD3’s precise function and associated mechanism of action in NPC have not yet been investigated. In this study, the expression of FOXD3 mRNA and protein was evaluated using RT-qPCR, western blotting, and immunohistochemistry. Protein levels involved in the phosphoinositide 3-kinase – protein kinase B (PI3K–Akt) pathway were assessed by western blot, and cell proliferation was determined by MTT and colony forming assays. Additionally, cell apoptosis was assessed by flow cytometric assay. Finally, the migration and invasion capabilities of the NPC cells were determined using wound healing and Transwell assays. We found that FOXD3 levels were relatively low in NPC tissue and cells, while an increase caused the inhibition of the PI3K–Akt pathway. Functional experiments found that overexpression of FOXD3 suppressed cell proliferation, migration, and invasion and enhanced cell apoptosis in NPC C6661 cells. IGF-1, an activator of the PI3K–Akt pathway, reversed the inhibitory effect of FOXD3. Furthermore, we found upregulation of the PI3K–Akt pathway and upregulation of the inhibitory effects of FOXD3 on C6661 cellular activities. In conclusion, FOXD3 negatively affected the PI3K–Akt pathway to restrain the processes involved in C6661 cell pathology. These findings further exposed the function and downstream axis of FOXD3 in NPC and displayed a promising new target for NPC therapy.

scholarly journals Antiproliferative Activity of Combined Biochanin A and Ginsenoside Rh2 on MDA-MB-231 and MCF-7 Human Breast Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2908 ◽  
Author(s):  
Guixing Ren ◽  
Zhenxing Shi ◽  
Cong Teng ◽  
Yang Yao
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Human Breast Cancer ◽  
Synergistic Effects ◽  
Inhibitory Effect ◽  
Biochanin A ◽  
Migration And Invasion ◽  
Ginsenoside Rh2 ◽  
Human Breast ◽  
Mcf 7

Breast cancer is the most frequently diagnosed cancer in women worldwide. The antiproliferative activities of biochanin A (BA) and ginsenoside Rh2 were determined by evaluating their inhibitory effect on MDA-MB-231 human breast cancer cell proliferation. The combination of BA with Rh2 was also assessed. In MDA cells, combination treatment led to a decrease in the EC50 values of BA and Rh2 to 25.20 μM and 22.75 μM, respectively. In MCF-7 cells, the EC50 values of combined BA and Rh2 decreased to 27.68 μM and 25.41 μM, respectively. BA combined with Rh2 also improved the inhibition of MDA-MB-231 and MCF-7 cell migration and invasion compared to the individual compounds. Western blot analysis demonstrated upregulation in p-p53, p-p38, and p-ASK1 proteins while levels of TRAF2 were downregulated. These results suggest that BA combined with Rh2 exhibits synergistic effects against MDA-MB-231 and MCF-7 cell proliferation.

scholarly journals RBFOX3 Regulates the Chemosensitivity of Cancer Cells to 5-Fluorouracil via the PI3K/AKT, EMT and Cytochrome-C/Caspase Pathways

2018 ◽  
Vol 46 (4) ◽  
pp. 1365-1380 ◽  
Author(s):  
Tianze Liu ◽  
Xiaojun Wu ◽  
Yizhuo Li ◽  
Wenjing Lu ◽  
Fufu Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cytochrome C ◽  
Rna Binding ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model ◽  
Hcc Cells

Background/Aims: RBFOX3, an RNA-binding fox protein, plays an important role in the differentiation of neuronal development, but its role in the chemosensitivity of hepatocellular carcinoma (HCC) to 5-FU is unknown. Methods: In this study, we examined the biological functions of RBFOX3 and its effect on the chemosensitivity of HCC cells to 5-FU in vitro and in a mouse xenograft model. Results: RBFOX3 was found to have elevated expression in HCC cell lines and tissue samples, and its knockdown inhibited HCC cell proliferation. Moreover, knockdown of RBFOX3 improved the inhibitory effect of 5-fluorouracil (5-FU) on cell proliferation, migration and invasion, and enhanced the apoptosis induced by 5-FU. However, overexpression of RBFOX3 reduced the inhibitory effect of 5-fluorouracil (5-FU) on cell proliferation, migration and invasion, and decreased the apoptosis induced by 5-FU. We further elucidated that RBFOX3 knockdown synergized with 5-FU to inhibit the growth and invasion of HCC cells through PI3K/AKT and epithelial-mesenchymal transition (EMT) signaling, and promote apoptosis by activating the cytochrome-c/caspase signaling pathway. Finally, we validated that RBFOX3 regulated 5-FU-mediated cytotoxicity in HCC in mouse xenograft models. Conclusions: The findings from this study indicate that RBFOX3 regulates the chemosensitivity of HCC to 5-FU in vitro and in vivo. Therefore, targeting RBFOX3 may improve the inhibition of HCC growth and progression by 5-FU, and provide a novel potential therapeutic strategy for HCC.

scholarly journals miR-103/miR-195/miR-15b Regulate SALL4 and Inhibit Proliferation and Migration in Glioma

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2938 ◽  
Author(s):  
Li-Ping Chen ◽  
Na-Na Zhang ◽  
Xue-Qing Ren ◽  
Jie He ◽  
Yu Li
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Glioma Cell ◽  
Inverse Correlation ◽  
Primary Brain Tumor ◽  
Migration And Invasion ◽  
Glioma Cell Proliferation ◽  
The Common ◽  
Direct Target ◽  
And Migration

Glioma is the common highly malignant primary brain tumor. However, the molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found that microRNA-103 (miR-103), microRNA-195 (miR-195), or microRNA-15b (miR-15b), which all have the same 5′ “seed” miRNA portion and share common binding sites in the SALL4 3′-untranslated region (UTR), were downregulated in glioma tissues and cell lines. These miRNAs suppressed glioma cell proliferation, migration, and invasion, induced cell apoptosis, and decreased the level of the SALL4 protein, but not that of SALL4 mRNA, which was identified as a direct target of all three miRNAs. The caspase-3/7 activity expression in U251 cells overexpressing these miRNAs was rescued during SALL4 upregulation. An obvious inverse correlation was observed between SALL4 and miR-103 or miR-195 expression levels in clinical glioma samples. Moreover, enforced expression of SALL4 stimulated cell proliferation, migration, and invasion. In conclusion, these data suggest that miR-103, miR-195, and miR-15b post-transcriptionally downregulated the expression of SALL4 and suppressed glioma cell growth, migration, and invasion, and increased cell apoptosis. These results provide a potential therapeutic target that may downregulate SALL4 in glioma.

scholarly journals LncRNA HOXA-AS2 Promotes Oral Squamous Cell Proliferation, Migration, and Invasion via Upregulating EZH2 as an Oncogene

2021 ◽  
Vol 20 ◽  
pp. 153303382110391
Author(s):  
Zhen Zhao ◽  
Yan Xing ◽  
Fei Yang ◽  
Zhijun Zhao ◽  
Yupeng Shen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell ◽  
Inhibitory Effect ◽  
G1 Phase ◽  
Migration And Invasion ◽  
Tunel Staining ◽  
Cell Cycle Distribution ◽  
Induce Cell Cycle Arrest ◽  
Invasion And Migration

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) serve important roles in the development of OSCC. The purpose of this study was to investigate the biological function and underlying regulatory mechanism of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) in OSCC. RT-qPCR was performed to analyze the HOXA-AS2 expressions in human immortalized oral epithelial cell (HIOEC) line, human OSCC cell lines, and plasma. The expression of HOXA-AS2 and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in Tca-8113 cells were knocked down or overexpressed by transfection with shRNA-HOXA-AS2 or pcDNA-EZH2, respectively. The interaction between HOXA-AS2 and EZH2 was validated by RNA immunoprecipitation assay. In addition, cell proliferation was assessed by CCK-8 and EdU assays. Cell cycle distribution was analyzed by flow cytometry. Cell migration and invasion were detected using wound healing and Transwell assays, respectively. Apoptosis was detected by TUNEL staining. The protein expression levels of cell cycle and apoptosis-related proteins were measured by western blot analysis. Compared with HIOEC cells, HOXA-AS2 expression in OSCC cells was upregulated. HOXA-AS2 knockdown significantly inhibited Tca-8113 cell proliferation, blocked the cell cycle by arresting cells in the G0/G1 phase, promoted apoptosis, and suppressed migration and invasion. In addition, HOXA-AS2 was predicted to directly target EZH2 and positively regulate EZH2 expression. EZH2 overexpression could reverse the inhibitory effect of HOXA-AS2 knockdown on the proliferation, migration, and invasion of Tca-8113 cells. In summary, the findings suggested that HOXA-AS2 may inhibit cell proliferation, invasion, and migration, induce cell cycle arrest in the G0/G1 phase, and increase cell apoptosis by targeting EZH2. The research indicated that HOXA-AS2/EZH2 axis may play a key role in the development of OSCC.

scholarly journals SPAG5 Is Involved in Human Gliomagenesis Through the Regulation of Cell Proliferation and Apoptosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunhong Wang ◽  
Haiyang Su ◽  
Rui Cheng ◽  
Hongming Ji
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Colony Formation ◽  
Glioma Cells ◽  
Clinical Intervention ◽  
Primary Brain Tumor ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Proliferation And Apoptosis

BackgroundGlioma is the most frequent malignant primary brain tumor in adults.ObjectiveTo explore the role of sperm-associated antigen 5 (SPAG5) in glioma.MethodsThe association between SPAG5 expression and clinical features was investigated based on The Cancer Genome Atlas (TCGA) datasets. The function of SPAG5 in glioma was analyzed using U87 and U251 cells. Knockdown glioma cells were constructed by shRNA interference. qRT-PCR and Western blotting were used to measure the expression of SPAG5 and Cadherin 2 (CDH2). Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, caspase 3/7 assay, and high-content screening (HCS) proliferation analysis and colony formation assay. Transwell assays and wound-healing assays were used to investigate cell migration and invasion.ResultsThe increased expression of SPAG5 was correlated with poor outcomes in glioma patients. Knocking down SPAG5 could inhibit the proliferation and colony formation and promoted the apoptosis of glioma cells. Knocking down SPAG5 could also inhibit cell migration and invasion and the expression of CDH2. Overexpression of CDH2 with SPAG5 depletion could restore the proliferation and inhibit the apoptosis of glioma cells, which also promoted cell migration and invasion.ConclusionsSPAG5 is a promising prognostic factor and potential therapeutic target for clinical intervention in glioma.

scholarly journals Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p

2018 ◽  
Vol 33 (2) ◽  
pp. 148-155 ◽  
Author(s):  
Qiang Meng ◽  
Bao-Ying Yang ◽  
Bei Liu ◽  
Ji-Xue Yang ◽  
Yang Sun
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Primary Brain Tumor ◽  
Normal Brain ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Glioma Cell Proliferation ◽  
Long Non Coding Rna

Introduction: Glioma is the most common primary brain tumor. The small nucleolar RNA host gene (SNHG) SNHG6 is a potential oncogene in the development of several types of cancers. Methods: In this study, we investigated the functional role of long non-coding RNA (lncRNA) SNHG6 in the malignancy of glioma in cell lines and transplanted nude mice. Results: We found that the expression of lncRNA SNHG6 was higher in glioma tissues and cells than in normal brain tissues and cells. The expression of lncRNA SNHG6 was positively correlated with the malignancy and poor prognosis of glioma patients. microRNA (miR)-101-3p expression was decreased in glioma tissues and cells and was negatively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of lncRNA SNHG6 was negatively correlated with the expression of miR-101-3p. SNHG6 contained a binding site of miR-101-3p. Knockdown of SNHG6 expression resulted in a significant increase of miR-101-3p expression. miR-101-3p mimic markedly decreased the luciferase activity of SNHG6. Knockdown of SNHG6 inhibited glioma cell proliferation, migration, and epithelial-mesenchymal transition (EMT), and increased apoptosis. miR-101-3p mimic enhanced knockdown of SNHG6-induced inhibition of cell proliferation, migration, and EMT, and an increase of apoptosis. Anti-miR-101-3p reversed the the effects of si-SNHG6 on cell malignancy. Knockdown of SNHG6 remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of SNHG6 increased the expression of miR-101-3p and reduced EMT biomarker expression. Conclusions: Our study provides novel insights into the functions of lncRNA SNHG6/miR-101-3p axis in the tumorigenesis of glioma.

scholarly journals Biological and physical approaches on the role of piplartine (piperlongumine) in cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tiago Henrique ◽  
Caroline de F. Zanon ◽  
Ana P. Girol ◽  
Ana Carolina Buzzo Stefanini ◽  
Nayara S. de A. Contessoto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
Physicochemical Analysis ◽  
Biologically Active ◽  
Migration And Invasion ◽  
Annexin A1 ◽  
Anti Inflammatory ◽  
Mimic Peptide

AbstractChronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.

scholarly journals Synergism between the phosphatidylinositol 3-kinase p110β isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hua-fu Zhao ◽  
Chang-peng Wu ◽  
Xiu-ming Zhou ◽  
Peng-yu Diao ◽  
Yan-wen Xu ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Nude Mice ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Combination Strategy ◽  
Combination Effects

Abstract Background Glioblastoma multiforme, the most aggressive and malignant primary brain tumor, is characterized by rapid growth and extensive infiltration to neighboring normal brain parenchyma. Our previous studies delineated a crosstalk between PI3K/Akt and JNK signaling pathways, and a moderate anti-glioblastoma synergism caused by the combined inhibition of PI3K p110β (PI3Kβ) isoform and JNK. However, this combination strategy is not potent enough. MLK3, an upstream regulator of ERK and JNK, may replace JNK to exert stronger synergism with PI3Kβ. Methods To develop a new combination strategy with stronger synergism, the expression pattern and roles of MLK3 in glioblastoma patient’s specimens and cell lines were firstly investigated. Then glioblastoma cells and xenografts in nude mice were treated with the PI3Kβ inhibitor AZD6482 and the MLK3 inhibitor URMC-099 alone or in combination to evaluate their combination effects on tumor cell growth and motility. The combination effects on cytoskeletal structures such as lamellipodia and focal adhesions were also evaluated. Results MLK3 protein was overexpressed in both newly diagnosed and relapsing glioblastoma patients’ specimens. Silencing of MLK3 using siRNA duplexes significantly suppressed migration and invasion, but promoted attachment of glioblastoma cells. Combined inhibition of PI3Kβ and MLK3 exhibited synergistic inhibitory effects on glioblastoma cell proliferation, migration and invasion, as well as the formation of lamellipodia and focal adhesions. Furthermore, combination of AZD6482 and URMC-099 effectively decreased glioblastoma xenograft growth in nude mice. Glioblastoma cells treated with this drug combination showed reduced phosphorylation of Akt and ERK, and decreased protein expression of ROCK2 and Zyxin. Conclusion Taken together, combination of AZD6482 and URMC-099 showed strong synergistic anti-tumor effects on glioblastoma in vitro and in vivo. Our findings suggest that combined inhibition of PI3Kβ and MLK3 may serve as an attractive therapeutic approach for glioblastoma multiforme.

Sign in / Sign up

Export Citation Format

Share Document