VWF Mediates Platelet Activation and Secretion to Promote Osteosarcoma Metastasis

Abstract [Background] As a multimer protein that mediates the adhesion of platelets to vascular surface, VWF has been found to participate in tumor metastasis, and may also be involved in the interaction between platelets and tumor cells. We observed in our clinical studies that the expression of VWF in lung metastatic osteosarcoma tumor is significantly higher than that of in primary osteosarcoma. Based on these observations, we speculate that VWF and platelets may contribute to promoting osteosarcoma metastasis. Thus, this study is to explore the effects of VWF-mediated platelet activation and secretion on the migration and invasion ability of SAOS2 cells with VWF-expressing osteosarcoma cell line SAOS2 as a model, as well as the inhibition of the interaction between VWF and platelets by specific antibodies. [Methods] SAOS2 cells were stimulated with inflammatory factor PMA and resulted in increased expression of vWF. Then the adhesion of labeled platelets to SAOS2 cells was evaluated under static and flow conditions, respectively. The above processes were intervened with SZ-2(anti-GPIb), SZ-123(anti-VWF) and AVW3 (anti-VWF) mAbs which specifically blocked the vWF-GPIbα pathway. Transwell assay was used to explore the effect of vWF-mediated migration and invasion ability of SAOS2 cells. PDGF-BB, TGF-β and VEGF that could be secreted by platelets to promote tumor cells growth in the co-culture system of platelets and SAOS2 cells were detected by ELISA. [Results] Under static and flow conditions, SAOS2 cells treated with PMA exhibited significantly higher platelets-adhesion capacity compared to the cells untreated with PMA, and the adhesion could be partially inhibited by SZ-2 and AVW3 mAbs. Furthermore, platelets significantly promoted the migration and invasion ability of SAOS2 cells, and PDGF-BB and TGF-β secreted by platelets were also increased in these processes. Both of SZ-2 and AVW3 mAbs partially decreased the migration and invasion ability of SAOS2 cells. [Conclusions] vWF were expressed highly in some kind of non-endothelial origin cancer cells, such as SAOS2, which mediates platelet activation and secreting factors such as PDGF-BB and TGF-β to promote tumor cells growth. Activated platelets have a significant promoted effect on the migration and invasion ability of SAOS2 cells and this process can be inhibited by antibodies that specifically block the pathway of VWF-GPIbα. Disclosures No relevant conflicts of interest to declare.

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IL-33/ST2 Axis Regulates Vasculogenic Mimicry via ERK1/2-MMP-2/9 Pathway in Melanoma

Dermatology ◽

10.1159/000498857 ◽

2019 ◽

Vol 235 (3) ◽

pp. 225-233 ◽

Cited By ~ 4

Author(s):

Fuhan Yang ◽

Mingming Wen ◽

Dayu Pan ◽

Xian Lin ◽

Jing Mo ◽

...

Keyword(s):

Tumor Cells ◽

Vasculogenic Mimicry ◽

Melanoma Cells ◽

Tube Formation ◽

Migration And Invasion ◽

Rapid Progression ◽

Inflammatory Factor ◽

Action Methods ◽

Significant Health

Background: Melanoma, an extremely malignant form of cancer, poses a significant health risk. Vasculogenic mimicry (VM), blood vessels formed by tumor cells instead of endothelial cells, is an important factor for the rapid progression of melanoma. Interleukin (IL)-33 is an inflammatory factor commonly found in the tumor microenvironment and plays an important role in the progression of many tumors. IL-33 acts on immune cells and tumor cells through its receptor ST2. This study hypothesized that IL-33 directly affects the progression of melanoma. Objectives: This study was designed to investigate the effect of IL-33 on VM of melanoma and its potential mechanism of action. Methods: The expression of ST2 was evaluated in 66 cases of melanoma collected from human patients, and the differences were analyzed. In vitro experiments were conducted to study the effects of the IL-33/ST2 axis on cell migration and invasion and to elucidate possible mechanisms. Results: ST2 expression is associated with that of matrix metalloproteinase (MMP)-2 and VM in melanoma of patients. IL-33 increases the abilities of proliferation, migration and invasion of melanoma cells and VM tube formation through ST2. IL-33 induces the production of MMP-2/9 via ERK1/2 phosphorylation. Conclusion: IL-33 can directly act on melanoma cells and promote its development.

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Platelets, Tumor Cell Invasiveness, and Metastasis

Blood ◽

10.1182/blood.v122.21.sci-31.sci-31 ◽

2013 ◽

Vol 122 (21) ◽

pp. SCI-31-SCI-31

Author(s):

Richard O. Hynes ◽

Shahinoor Begum ◽

Myriam Labelle

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Conflicts Of Interest ◽

Cell Types ◽

Therapeutic Interventions ◽

Migration And Invasion ◽

Cell Contact ◽

Cell Arrest

Abstract Platelets have long been known to promote metastasis, and multiple mechanisms have been proposed to explain this phenomenon, including adhesion, coagulation, and protection against natural killer (NK) cells or turbulence. One mechanism that has been little explored is the possibility that platelets might secrete growth factors or provide other stimuli that could enhance the malignant properties of tumor cells. We have shown that pretreatment of carcinoma cells with platelets induces an EMT-like transformation in their properties in vitro and renders them much more metastatic after introduction into mice. TGF-β, produced by platelets and released on their activation is essential for both the in vitro and the in vivo effects. However, TGF-β alone is insufficient; platelet-tumor cell contact is also required and this contact activates NFkB signaling, which synergizes with the TGF-β signaling. Both signals are required for the enhancement of metastasis. In addition to enhancing migration and invasion in vitro, platelets enhance extravasation in vivo. Earlier work has shown that both P-selectin (expressed on platelets) and L-selectin (expressed on leukocytes) are essential for efficient metastasis, and aggregates of tumor cells, platelets, and leukocytes can be observed at sites of tumor cell arrest and extravasation. It has also been demonstrated by others that leukocytes can enhance extravasation and metastatic seeding. Therefore, we have been interested in the question of the relative roles of platelets and leukocytes in these processes. Which cell types are recruited at the sites of metastatic seeding? Does one cell type depend on another? Which cell types enhance metastasis? What roles do the platelets play in recruiting the other cell types? The involvement of platelets in enhancing metastasis also raises questions about the effects of platelets on circulating tumor cells (CTCs). Could platelets enhance the metastatic capacity of CTCs? Could it be the case that only those CTCs that are associated with platelets and/or leukocytes are functionally involved in seeding metastases? Such aggregates are not scored in most current assays for CTCs and will require new investigative approaches. Platelet participation in metastasis also raises the possibility of therapeutic interventions targeting platelet-specific targets and the paracrine interactions between them and other cells. Disclosures: No relevant conflicts of interest to declare.

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CXCL13/CXCR5 Interaction Facilitates VCAM-1-Dependent Migration in Human Osteosarcoma

International Journal of Molecular Sciences ◽

10.3390/ijms21176095 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6095 ◽

Cited By ~ 1

Author(s):

Ju-Fang Liu ◽

Chiang-Wen Lee ◽

Chih-Yang Lin ◽

Chia-Chia Chao ◽

Tsung-Ming Chang ◽

...

Keyword(s):

Cell Migration ◽

Metastatic Potential ◽

Nuclear Factor Κb ◽

Vital Role ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Human Osteosarcoma ◽

Kinase C ◽

Metastatic Osteosarcoma ◽

Cell Adhesion Molecule 1

Osteosarcoma is the most common primary tumor of the skeletal system and is well-known to have an aggressive clinical outcome and high metastatic potential. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays a vital role in the development of several cancers. However, the effect of CXCL13 in the motility of osteosarcoma cells remains uncertain. Here, we found that CXCL13 increases the migration and invasion potential of three osteosarcoma cell lines. In addition, CXCL13 expression was upregulated in migration-prone MG-63 cells. Vascular cell adhesion molecule 1 (VCAM-1) siRNA and antibody demonstrated that CXCL13 promotes migration via increasing VCAM-1 production. We also show that CXCR5 receptor controls CXCL13-mediated VCAM-1 expression and cell migration. Our study identified that CXCL13/CXCR5 axis facilitate VCAM-1 production and cell migration in human osteosarcoma via the phospholipase C beta (PLCβ), protein kinase C α (PKCα), c-Src, and nuclear factor-κB (NF-κB) signaling pathways. CXCL13 and CXCR5 appear to be a novel therapeutic target in metastatic osteosarcoma.

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TNF-Induced Vaso-Occlusive and Inflammatory Processes in Mice with Sickle Cell Anemia Are Abrogated By the Platelet Activation Inhibitor, Prasugrel

Blood ◽

10.1182/blood-2018-99-118633 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2354-2354

Author(s):

Hanan Chweih ◽

Juliete A.F. Silva ◽

Erica M.F. Gotardo ◽

Pamela L. Brito ◽

Guilherme G.O. Barbosa ◽

...

Keyword(s):

Blood Flow ◽

Platelet Activation ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Conflicts Of Interest ◽

Chronic Administration ◽

Vascular Wall ◽

Acute Administration ◽

Inflammatory Stimuli ◽

Adhesion Of Platelets

Abstract Background: Vaso-occlusive processes in sickle cell anemia (SCA) are triggered by inflammatory molecules, along with pancellular activation and the recruitment and adhesion of leukocytes to the endothelium. Interactions between platelets, neutrophils, and erythrocytes are observed in the SCA circulation, but the exact role of platelets in the initiation and propagation of vaso-occlusion is not well understood. Aim: We, herein, evaluated the effects of the inhibition of platelet activation on TNF-α (TNF)-triggered vaso-occlusive processes in the microcirculation of mice with SCA, using prasugrel, a platelet ADP P2Y12 receptor inhibitor. Methods: Chimeric male control (CON) and SCA (SCA) mice received prasugrel (1 mg/kg, by gavage) or vehicle (saline) in a single administration, 1h prior to TNF (0.5 μg/g, i.p). In some experiments, 1 mg/kg prasugrel was administered chronically for 5x per week for 4 weeks. Following i.v. injection of anti-CD41 PE, anti-CD45 PeCy-5 and anti-Ly6G Alexa 488 antibodies for labeling platelets, leukocytes (in general) and neutrophils respectively, the cremaster muscle was exposed and the microcirculation was observed by conventional and confocal intravital microscopy. Results: While the acute administration of prasugrel to CON and SCA mice did not alter the quantity of platelets in the microcirculation (data not shown), it significantly reduced the adhesion of platelets to the vascular wall in both CON animals (12±1.6 vs 5.7±1.4 % adhered of total platelets, n=3; p<0.05) and SCA mice after TNF (36.2±7.1 vs 4.8±2.5 % platelets adhered for w/out and with prasugrel, respectively; n=3; p<0.0001) (see Figure). Furthermore, prasugrel significantly reduced the number of platelet/neutrophil aggregates in TNF-treated CON (2.7±0.4 vs 0.53±0.3 aggregates adhered 100 µm−1, p<0.001 n=3) and SCA mice (3.1±0.7 vs 0.76±0.3 aggregates adhered 100 µm−1, p<0.01 n=3), and also platelet/non-neutrophil leukocytes in CON (1.3±0.7 vs 0.2±0.1 aggregates adhered 100 µm−1, p<0.01 n=3) and SCA mice (2.0±0.3 vs 0.2±0.1 aggregates adhered 100 µm−1, p<0.001 n=3). Alterations in platelet adhesion to the vascular wall and platelet-leukocyte aggregate formation were accompanied by reductions in the recruitment of leukocytes to the venule walls, after prasugrel administration. Prasugrel significantly decreased the rolling, adhesion and extravasation of leukocytes in both CON (4.9±2.7 vs 1.14±0.5 min−1; 9.2±0.8 vs 2.7±0.5 100 µm−1; 1.9±0.3 vs 0.4±0.1 100x50 µm-2; for w/out and with prasugrel, respectively; n=3; p<0.001) and SCA mice (36.0±3.0 vs 3.0±0.6 min−1; 16.6±1.5 vs 6.4±1.2 100 µm−1; 6.9±0.8 vs 1.7±0.4 100x50 µm-2; for w/out and with prasugrel, respectively; n=3; p<0.0001). Acute prasugrel treatment also increased blood flow velocity after TNF stimulation in CON mice (37±10 vs 110±35 mm3/s, p<0.01, n=3) and substantially augmented flow in SCA mice (13±2 vs 94±12 mm3/s, p<0.0001, n=3), approaching flow velocities similar to those observed in control animals that had not received TNF (Data not shown). The survival of SCA animals treated with a single dose of prasugrel increased by 1.3 hours compared to the SCA animals that received the vehicle (n=3, p<0.05). Complimentary experiments demonstrated a similar effect of the chronic administration of prasugrel, which significantly reduced leukocyte recruitment to the vascular wall after TNF in both CON and SCA mice (data not shown, P<0.05). Conclusions: Our findings show that the inhibition of platelet activation by prasugrel, while significantly decreasing the adhesion of platelets to venules walls and the formation of heterocellular aggregates, was able to almost abolish the recruitment of leukocytes to the microcirculation of SCA mice after an inflammatory stimulus. This reduction in platelet and leukocyte vascular recruitment was associated with major improvements in blood flow and in the survival of animals with SCA. Thus, our data suggest that platelet activation and the consequent adhesion of platelets to the vascular wall is a fundamental step in the initiation of the vaso-occlusive process in response to inflammatory stimuli. Our findings support further investigations into the use of drugs that inhibit platelet activation (including prasugrel itself) as a therapeutic approach for SCA. Disclosures No relevant conflicts of interest to declare.

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Thrombus formation on artificial surfaces: Correlative microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010016176x ◽

1990 ◽

Vol 48 (3) ◽

pp. 840-841

Author(s):

Quintin J. Lai ◽

Stuart L. Cooper ◽

Ralph M. Albrecht

Keyword(s):

Electron Microscopy ◽

High Resolution ◽

Low Voltage ◽

Thrombus Formation ◽

Blood Platelets ◽

Polymer Surfaces ◽

Flow Conditions ◽

Transmission Electron ◽

Adhesion Of Platelets ◽

Microscopic Techniques

Thrombus formation and embolization are significant problems for blood-contacting biomedical devices. Two major components of thrombi are blood platelets and the plasma protein, fibrinogen. Previous studies have examined interactions of platelets with polymer surfaces, fibrinogen with platelets, and platelets in suspension with spreading platelets attached to surfaces. Correlative microscopic techniques permit light microscopic observations of labeled living platelets, under static or flow conditions, followed by the observation of identical platelets by electron microscopy. Videoenhanced, differential interference contrast (DIC) light microscopy permits high-resolution, real-time imaging of live platelets and their interactions with surfaces. Interference reflection microscopy (IRM) provides information on the focal adhesion of platelets on surfaces. High voltage, transmission electron microscopy (HVEM) allows observation of platelet cytoskeletal structure of whole mount preparations. Low-voltage, high resolution, scanning electron microscopy allows observation of fine surface detail of platelets. Colloidal gold-labeled fibrinogen, used to identify the Gp Ilb/IIIa membrane receptor for fibrinogen, can be detected in all the above microscopies.

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Dehydroandrographolide Inhibits Osteosarcoma Cell Growth and Metastasis by Targeting SATB2-mediated EMT

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190705121614 ◽

2019 ◽

Vol 19 (14) ◽

pp. 1728-1736

Author(s):

Xuefeng Liu ◽

Yonggang Fan ◽

Jing Xie ◽

Li Zhang ◽

Lihua Li ◽

...

Keyword(s):

Cell Cycle ◽

Wound Healing ◽

Cell Growth ◽

Brdu Incorporation ◽

Migration And Invasion ◽

Therapeutic Drug ◽

Osteosarcoma Cell ◽

Dependent Manner ◽

Inhibition Of Proliferation ◽

Predominant Component

Background:The 12-hydroxy-14-dehydroandrographolide (DP) is a predominant component of the traditional herbal medicine Andrographis paniculata (Burm. f.) Nees (Acanthaceae). Recent studies have shown that DP exhibits potent anti-cancer effects against oral and colon cancer cells.Objective:This investigation examined the potential effects of DP against osteosarcoma cell.Methods:A cell analyzer was used to measure cell viability. The cell growth and proliferation were performed by Flow cytometry and BrdU incorporation assay. The cell migration and invasion were determined by wound healing and transwell assay. The expression of EMT related proteins was examined by Western blot analysis.Results:In this study, we found that DP treatment repressed osteosarcoma (OS) cell growth in a dose-dependent manner. DP treatment significantly inhibited OS cell proliferation by arresting the cell cycle at G2/M phase. In addition, DP treatment effectively inhibited the migration and invasion abilities of OS cells through wound healing and Transwell tests. Mechanistic studies revealed that DP treatment effectively rescued the epithelialmesenchymal transition (EMT), while forced expression of SATB2 in OS cells markedly reversed the pharmacological effect of DP on EMT.Conclusion:Our data demonstrated that DP repressed OS cell growth through inhibition of proliferation and cell cycle arrest; DP also inhibited metastatic capability of OS cells through a reversal of EMT by targeting SATB2. These findings demonstrate DP’s potential as a therapeutic drug for OS treatment.

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Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

Discover Oncology ◽

10.1007/s12672-021-00415-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zehua Zhang ◽

Fei Dai ◽

Fei Luo ◽

Wenjie Wu ◽

Shuai Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Therapy ◽

Disease Free Survival ◽

Tumor Stage ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Proliferation And Metastasis ◽

New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

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The cancer glycocalyx mediates intravascular adhesion and extravasation during metastatic dissemination

Communications Biology ◽

10.1038/s42003-021-01774-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Giovanni S. Offeddu ◽

Cynthia Hajal ◽

Colleen R. Foley ◽

Zhengpeng Wan ◽

Lina Ibrahim ◽

...

Keyword(s):

Hyaluronic Acid ◽

Tumor Cells ◽

Cancer Progression ◽

Vascular System ◽

Migration And Invasion ◽

Improve Patient Survival ◽

Adhesive Interactions ◽

Vitro Model ◽

Metastatic Sites

AbstractThe glycocalyx on tumor cells has been recently identified as an important driver for cancer progression, possibly providing critical opportunities for treatment. Metastasis, in particular, is often the limiting step in the survival to cancer, yet our understanding of how tumor cells escape the vascular system to initiate metastatic sites remains limited. Using an in vitro model of the human microvasculature, we assess here the importance of the tumor and vascular glycocalyces during tumor cell extravasation. Through selective manipulation of individual components of the glycocalyx, we reveal a mechanism whereby tumor cells prepare an adhesive vascular niche by depositing components of the glycocalyx along the endothelium. Accumulated hyaluronic acid shed by tumor cells subsequently mediates adhesion to the endothelium via the glycoprotein CD44. Trans-endothelial migration and invasion into the stroma occurs through binding of the isoform CD44v to components of the sub-endothelial extra-cellular matrix. Targeting of the hyaluronic acid-CD44 glycocalyx complex results in significant reduction in the extravasation of tumor cells. These studies provide evidence of tumor cells repurposing the glycocalyx to promote adhesive interactions leading to cancer progression. Such glycocalyx-mediated mechanisms may be therapeutically targeted to hinder metastasis and improve patient survival.

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Emerging roles of cancer-testis antigenes, semenogelin 1 and 2, in neoplastic cells

Cell Death Discovery ◽

10.1038/s41420-021-00482-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Oleg Shuvalov ◽

Alyona Kizenko ◽

Alexey Petukhov ◽

Olga Fedorova ◽

Alexandra Daks ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Reproductive System ◽

Seminal Fluid ◽

Cancer Development ◽

Migration And Invasion ◽

Malignant Cells ◽

Cancer Testis

AbstractCancer-testicular Antigens (CTAs) belong to a group of proteins that under normal conditions are strictly expressed in a male’s reproductive tissues. However, upon malignisation, they are frequently re-expressed in neoplastic tissues of various origin. A number of studies have shown that different CTAs affect growth, migration and invasion of tumor cells and favor cancer development and metastasis. Two members of the CTA group, Semenogelin 1 and 2 (SEMG1 and SEMG2, or SEMGs) represent the major component of human seminal fluid. They regulate the motility and capacitation of sperm. They are often re-expressed in different malignancies including breast cancer. However, there is almost no information about the functional properties of SEMGs in cancer cells. In this review, we highlight the role of SEMGs in the reproductive system and also summarize the data on their expression and functions in malignant cells of various origins.

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Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function

International Journal of Molecular Sciences ◽

10.3390/ijms22062982 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2982

Author(s):

Kyeongmin Kim ◽

Sungmin Lee ◽

Hyunkoo Kang ◽

Eunguk Shin ◽

Hae Yu Kim ◽

...

Keyword(s):

Tumor Cells ◽

Metabolic Flux ◽

Mitochondrial Fission ◽

Mammalian Target Of Rapamycin ◽

Primary Brain Tumor ◽

Metabolic Reprogramming ◽

Migration And Invasion ◽

Mitochondrial Morphology ◽

Dual Specificity ◽

Novel Strategy

Glioblastoma multiforme (GBM) is a malignant primary brain tumor with poor patient prognosis. Although the standard treatment of GBM is surgery followed by chemotherapy and radiotherapy, often a small portion of surviving tumor cells acquire therapeutic resistance and become more aggressive. Recently, altered kinase expression and activity have been shown to determine metabolic flux in tumor cells and metabolic reprogramming has emerged as a tumor progression regulatory mechanism. Here we investigated novel kinase-mediated metabolic alterations that lead to acquired GBM radioresistance and malignancy. We utilized transcriptomic analyses within a radioresistant GBM orthotopic xenograft mouse model that overexpresses the dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3). We find that within GBM cells, radiation exposure induces DYRK3 expression and DYRK3 regulates mammalian target of rapamycin complex 1 (mTORC1) activity through phosphorylation of proline-rich AKT1 substrate 1 (PRAS40). We also find that DYRK3 knockdown inhibits dynamin-related protein 1 (DRP1)-mediated mitochondrial fission, leading to increased oxidative phosphorylation (OXPHOS) and reduced glycolysis. Importantly, enforced DYRK3 downregulation following irradiation significantly impaired GBM cell migration and invasion. Collectively, we suggest DYRK3 suppression may be a novel strategy for preventing GBM malignancy through regulating mitochondrial metabolism.

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