14 results on '"Mohyeldin, Ahmed"'
Search Results
2. When a Meningioma Isn't: Endoscopic Endonasal Orbital Decompression and Biopsy of Skull Base Rosai-Dorfman Disease Treated Previously with Empiric Radiation Therapy.
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Shah, Varun, Mohyeldin, Ahmed, London, Nyall R., Fritz, Joel, Prevedello, Daniel M., Carrau, Ricardo L., and Hardesty, Douglas A.
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SKULL base , *NON-langerhans-cell histiocytosis , *MENINGIOMA , *RADIOTHERAPY , *CENTRAL nervous system , *EOSINOPHILIC granuloma , *THYROID eye disease - Abstract
Rosai-Dorfman disease (RDD) is a rare, benign histiocytosis disorder with only approximately 100 reported central nervous system cases in the literature. Even less common is skull base involvement of RDD, with about 41 reported cases. Radiographically, RDD can appear similar to a meningioma; the true diagnosis is only found with histologic analysis. Although "benign," RDD can lead to significant neurologic morbidity from the disease or unnecessary surgical and nonsurgical treatment. While rare, intracranial RDD has been treated with chemotherapy or radiotherapy, with surgery playing a limited role to relieve mass effect. Surgical approaches to the skull base are invasive and pose risk, especially for a benign and self-limiting disease like RDD. Here we present the case of a 63-year-old woman with a presumed spheno-orbital meningioma for which the patient previously underwent radiation therapy. On presentation to our facility, the patient noted pressure headaches and blurry vision, and imaging demonstrated progression of her disease. For these reasons, surgical debulking and biopsy were undertaken. This report demonstrates the role of EEA for tissue biopsy and decompression of the affected cranial nerves and orbit. This paradigm seems to provide a safe and effective way to manage patients with compressive symptoms, while also allowing for tissue sampling. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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3. Brachyury-YAP Regulatory Axis Drives Stemness and Growth in Cancer.
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Shah, Sagar R., David, Justin M., Tippens, Nathaniel D., Mohyeldin, Ahmed, Martinez-Gutierrez, Juan C., Ganaha, Sara, Schiapparelli, Paula, Hamilton, Duane H., Palena, Claudia, Levchenko, Andre, and Quiñones-Hinojosa, Alfredo
- Abstract
Summary Molecular factors that define stem cell identity have recently emerged as oncogenic drivers. For instance, brachyury, a key developmental transcriptional factor, is also implicated in carcinogenesis, most notably of chordoma, through mechanisms that remain elusive. Here, we show that brachyury is a crucial regulator of stemness in chordoma and in more common aggressive cancers. Furthermore, this effect of brachyury is mediated by control of synthesis and stability of Yes-associated protein (YAP), a key regulator of tissue growth and homeostasis, providing an unexpected mechanism of control of YAP expression. We further demonstrate that the brachyury-YAP regulatory pathway is associated with tumor aggressiveness. These results elucidate a mechanism of controlling both tumor stemness and aggressiveness through regulatory coupling of two developmental factors. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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4. Sinonasal morbidity following endoscopic endonasal skull base surgery.
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Awad, Ahmed J., Mohyeldin, Ahmed, El-Sayed, Ivan H., and Aghi, Manish K.
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ENDOSCOPIC surgery , *BRAIN surgery , *PEDIATRICS , *QUALITY of life , *SKULL base - Abstract
Open transcranial surgery has long served as the traditional approach for resecting tumors and other lesions in the skull base. However, endoscopic endonasal skull base surgery (EESBS) has emerged as a credible alternative. This paper provides insight on the sinonasal morbidity in patients undergoing EESBS. A literature review was performed by searches of MEDLINE database to provide further insight on sinonasal morbidity associated with EESBS, with a particular focus on published incidence rates and patterns of complication. We identified only articles that reported the incidence of sinonasal morbidity and complications as the major outcome of the studies. The most common sinonasal morbidity symptoms are nasal crusting (50.8%), nasal discharge (40.4%), nasal airflow blockage (40.1%) followed by disturbances in olfaction (26.7%). The incidence of mucocele formation is 8%, and this is significantly increased in pediatric patients up to 25% (range, 14-50%). Epistaxis appears to be a rare event, often times not found in some case series. Some studies suggested less morbidity if the middle turbinate can be preserved, a finding that must be balanced with the need for sufficient exposure on larger cases. Sinonasal morbidity following endoscopic endonasal skull base surgery has the potential to adversely impact patient quality of life, with nasal crusting and discharge being the two most common symptoms. Morbidity signs and symptoms usually resolve within 3-4 months, however symptoms can persist for longer with more complex surgeries. The rate of mucocele formation is higher in pediatric patients, with special attention required in graft positioning for this population in particular. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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5. Pyruvate Dehydrogenase Complex Activity Controls Metabolic and Malignant Phenotype in Cancer Cells.
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McFate, Thomas, Mohyeldin, Ahmed, Huasheng Lu, Thakar, Jay, Henriques, Jeremy, Halim, Nader D., Hong Wu, Schell, Michael J., Tsz Mon Tsang, Teahan, Orla, Shaoyu Zhou, Califano, Joseph A., Nam Ho Jeoung, Harris, Robert A., and Verma, Ajay
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GENOTYPE-environment interaction , *DEHYDROGENASES , *BIOCHEMISTRY , *TRANSCRIPTION factors , *SQUAMOUS cell carcinoma , *PHOTOSYNTHETIC oxygen evolution - Abstract
High lactate generation and low glucose oxidation, despite normal oxygen conditions, are commonly seen in cancer cells and tumors. Historically known as the Warburg effect, this altered metabolic phenotype has long been correlated with malignant progression and poor clinical outcome. However, the mechanistic relationship between altered glucose metabolism and malignancy remains poorly understood. Here we show that inhibition of pyruvate dehydrogenase complex (PDC) activity contributes to the Warburg metabolic and malignant phenotype in human head and neck squamous cell carcinoma. PDC inhibition occurs via enhanced expression of pyruvate dehydrogenase kinase-1 (PDK-1), which results in inhibitory phosphorylation of the pyruvate dehydrogenase a (PDHα) subunit. We also demonstrate that PDC inhibition in cancer cells is associated with normoxic stabilization of the malignancy-promoting transcription factor hypoxia-inducible factor-1α (HIF-1α) by glycolytic metabolites. Knockdown of PDK-1 via short hairpin RNA lowers PDHα phosphorylation, restores PDC activity, reverts the Warburg metabolic phenotype, decreases normoxic HIF-1α expression, lowers hypoxic cell survival, decreases invasiveness, and inhibits tumor growth. PDK-1 is an HIF-1-regulated gene, and these data suggest that the buildup of glycolytic metabolites, resulting from high PDK-l expression, may in turn promote HIF-1 activation, thus sustaining a feed-forward loop for malignant progression. In addition to providing anabolic support for cancer cells, altered fuel metabolism thus supports a malignant phenotype. Correction of metabolic abnormalities offers unique opportunities for cancer treatment and may potentially synergize with other cancer therapies. [ABSTRACT FROM AUTHOR]
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- 2008
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6. Erythropoietin Signaling Promotes Invasiveness of Human Head and Neck Squamous Cell Carcinoma.
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Mohyeldin, Ahmed, Huasheng Lu, Dalgard, Clifton, Lai, Stephen Y., Cohen, Noam, Acs, Geza, and Verma, Ajay
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ERYTHROPOIETIN , *COLONY-stimulating factors (Physiology) , *ANEMIA , *CANCER patients , *HEMATOPOIETIC growth factors - Abstract
Erythropoietin (Epo) is used for managing anemia in cancer patients. However, recent studies have raised concerns for this practice. We investigated the expression and function of Epo and the erythropoietin receptor (EpoR) in tumor biopsies and cell lines from human head and neck cancer. Epo responsiveness of the cell lines was assessed by Epoetin-α-induced tyrosine phosphorylation of the Janus kinase 2 (JAK2) protein kinase. Transmigration assays across Matrigel-coated filters were used to examine the effects of Epoetin-α on cell invasiveness. In 32 biopsies, we observed a significant association between disease progression and expression of Epo and its receptor, EpoR. Expression was highest in malignant cells, particularly within hypoxic and infiltrating tumor regions. Although both Epo and EpoR were expressed in human head and neck carcinoma cell lines, only EpoR was upregulated by hypoxia. Epoetin-α treatment induced prominent JAK2 phosphorylation and enhanced cell invasion. Inhibition of JAK2 phosphorylation reduced both basal and Epo-induced invasiveness. Our findings support a role for autocrine or paracrine Epo signaling in the malignant progression and local invasiveness of head and neck cancer. This mechanism may also be activated by recombinant Epo therapy and could potentially produce detrimental effects in rhEpo-treated cancer patients. [ABSTRACT FROM AUTHOR]
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- 2005
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7. Phenotypic Plasticity of Invasive Edge Glioma Stem-like Cells in Response to Ionizing Radiation.
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Minata, Mutsuko, Audia, Alessandra, Shi, Junfeng, Lu, Songjian, Bernstock, Joshua, Pavlyukov, Marat S., Das, Arvid, Kim, Sung-Hak, Shin, Yong Jae, Lee, Yeri, Koo, Harim, Snigdha, Kirti, Waghmare, Indrayani, Guo, Xing, Mohyeldin, Ahmed, Gallego-Perez, Daniel, Wang, Jia, Chen, Dongquan, Cheng, Peng, and Mukheef, Farah
- Abstract
Summary Unresectable glioblastoma (GBM) cells in the invading tumor edge can act as seeds for recurrence. The molecular and phenotypic properties of these cells remain elusive. Here, we report that the invading edge and tumor core have two distinct types of glioma stem-like cells (GSCs) that resemble proneural (PN) and mesenchymal (MES) subtypes, respectively. Upon exposure to ionizing radiation (IR), GSCs, initially enriched for a CD133
+ PN signature, transition to a CD109+ MES subtype in a C/EBP-β-dependent manner. Our gene expression analysis of paired cohorts of patients with primary and recurrent GBMs identified a CD133-to-CD109 shift in tumors with an MES recurrence. Patient-derived CD133− /CD109+ cells are highly enriched with clonogenic, tumor-initiating, and radiation-resistant properties, and silencing CD109 significantly inhibits these phenotypes. We also report a conserved regulation of YAP/TAZ pathways by CD109 that could be a therapeutic target in GBM. Graphical Abstract Highlights • Distinct types of GSCs exist in the GBM core versus the invasive edge • Gain of CD109 in tumor cells occurs at the invasive edge in response to IR • IR induced pro-inflammatory response transcriptionally regulates CD109 via C/EBP-β • CD109 drives oncogenic signaling through the YAP/TAZ pathway Minata et al., in response to the proinflammatory environment induced by radiation, find that the tumor cells at the invasive edge acquire the expression of the CD109 protein concomitantly losing CD133. CD109 drives oncogenic signaling through the YAP/TAZ pathway, confers radioresistance to the cells, and represents a new potential therapeutic target for glioblastoma. [ABSTRACT FROM AUTHOR]- Published
- 2019
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8. Lower Extremity Paralysis After Radiofrequency Ablation of Vertebral Metastases.
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Huntoon, Kristin, Eltobgy, Mostafa, Mohyeldin, Ahmed, and Elder, J. Bradley
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PARAPLEGIA , *CATHETER ablation , *BONE metastasis , *METASTASIS , *MAGNETIC resonance imaging , *PATHOLOGIC neovascularization - Abstract
Radiofrequency ablation (RFA) focally destroys abnormal or dysfunctional tissue using thermal energy generated from alternating current. The utilization of RFA has gained popularity as a minimally invasive procedure for the treatment of skeletal metastases with a particular focus on palliative pain treatments to the spine, pelvis, long bones, sternum, and glenoid. More recently, single-session procedures that combine RFA with vertebral augmentation techniques have allowed treatment to areas of pain associated with pathologic fractures secondary to metastatic disease. Although many studies have been done to investigate the safety and efficacy of RFA, there have been no reported cases to date in which the use of RFA for the treatment of spinal metastases has led to any major permanent neurological injury. This report describes a case of a 61-year-old woman who underwent RFA and kyphoplasty for spinal metastases and noted the immediate onset of lower extremity paralysis after the procedure. To the best of our knowledge, this is the first documented case of permanent lower extremity paralysis in the medical literature after radiofrequency thermal ablation of spine metastases. Postoperative magnetic resonance imaging and physical examination suggest RFA-induced thermal injury as the most likely mechanism of paralysis. In this report, a review of previous in vivo models used in studying the efficacy and safety of spine RFA is conducted. Additionally, the literature has been reviewed for any neurological events reported with the use of RFA in the treatment of patients with vertebral pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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9. Endoscopic versus Nonendoscopic Surgery for Resection of Craniopharyngiomas.
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Abiri, Arash, Roman, Kelsey M., Latif, Kareem, Goshtasbi, Khodayar, Torabi, Sina J., Lehrich, Brandon M., Mohyeldin, Ahmed, Hsu, Frank P.K., and Kuan, Edward C.
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CRANIOPHARYNGIOMA , *SURGICAL excision , *SURVIVAL rate , *OVERALL survival , *ODDS ratio , *LOGISTIC regression analysis , *ENDOSCOPIC surgery - Abstract
While surgery is a critical treatment option for craniopharyngiomas, the optimal surgical approach remains under debate. Herein, we studied a large cohort of craniopharyngioma patients to identify predictors of endoscopic surgery (ES) and to compare survival outcomes between patients undergoing ES versus nonendoscopic surgery (NES). The National Cancer Database was queried for patients receiving definitive surgical treatment in 2010–2016. Cox proportional hazards and propensity score-adjusted Kaplan–Meier analyses assessed mortality risk and overall survival, respectively. Predictors of surgical approach were evaluated via logistic regression. Of 1721 patients, 508 (29.5%) underwent ES, 877 (50.9%) were female, and the average age was 41.8 ± 21.3 years. Matched ES and NES cohorts exhibited 5-year overall survival rates of 88.0% and 79.8%, respectively (P = 0.004). ES was associated with reduced mortality (Hazard Ratio = 0.634; 95% confidence interval [CI], 0.439–0.914; P = 0.015). Patients treated at academic facilities (Odds Ratio [OR] = 2.095; 95% CI, 1.529–2.904; P < 0.001) or diagnosed recently (OR = 1.132; 95% CI, 1.058–1.211; P < 0.001) were more likely to undergo ES, while those with tumor sizes >3 cm (OR = 0.604; 95% CI, 0.451–0.804; P < 0.001) or receiving adjuvant radiotherapy (OR = 0.641; 95% CI, 0.454–0.894; P = 0.010) were more likely to receive NES. Surgical inpatient stays were significantly shorter with ES compared to NES (8.0 vs. 10.5 days, P < 0.001). On linear regression, ES usage increased by 82.4% and NES usage decreased by 23.4% between 2010 and 2016 (R2 = 0.575, P = 0.031). ES of craniopharyngioma was associated with reduced mortality and shorter inpatient stays compared to NES. Factors including tumor size, extent of resection, facility type, and year of diagnosis may predict receiving ES. There is a trend towards increased usage of ES for surgical management of craniopharyngiomas. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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10. Untitled.
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Mohyeldin, Ahmed and Prevedello, Daniel M.
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SCIENTISTS , *DIAGNOSTIC imaging - Published
- 2019
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11. Reversible Inactivation of HIF-1 Prolyl Hydroxylases Allows Cell Metabolism to Control Basal HIF-1.
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Huasheng Lu, Dalgard, Clifton L., Mohyeldin, Ahmed, McFate, Thomas, Tait, A. Sasha, and Verma, Ajay
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PROLINE hydroxylase , *OXIDOREDUCTASES , *CELL metabolism , *CELL respiration , *CELLULAR control mechanisms , *BASAL metabolism , *BLOOD-vessel development , *PROTEOMICS , *TRANSCRIPTION factors - Abstract
Continuous hydroxylation of the HIF-1 transcription factor a subunit by oxygen and 2-oxoglutarate-dependent dioxygenases promotes decay of this protein and thus prevents the transcriptional activation of many genes involved in energy metabolism, angiogenesis, cell survival, and matrix modification. Hypoxia blocks HIF-1α hydroxylation and thus activates HIF-1α-mediated gene expression. Several nonhypoxic stimuli can also activate HIF-1, although the mechanisms involved are not well known. Here we show that the glucose metabolites pyruvate and oxaloacetate inactivate HIF-1α decay in a manner selectively reversible by ascorbate, cysteine, histidine, and ferrous iron but not by 2-oxoglutarate or oxygen. Pyruvate and oxaloacetate bind to the 2-oxoglutarate site of HIF-1α prolyl hydroxylases, but their effects on HIF-1 are not mimicked by other Krebs cycle intermediates, including succinate and fumarate. We show that inactivation of HIF-1 hydroxylation by glucose-derived 2-oxoacids underlies the prominent basal HIF-1 activity commonly seen in many highly glycolytic cancer cells. Since HIF-1 itself promotes glycolytic metabolism, enhancement of HIF-1 by glucose metabolites may constitute a novel feed-forward signaling mechanism involved in malignant progression. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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12. Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent Manner.
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Kim, Sung-Hak, Ezhilarasan, Ravesanker, Phillips, Emma, Gallego-Perez, Daniel, Sparks, Amanda, Taylor, David, Ladner, Katherine, Furuta, Takuya, Sabit, Hemragul, Chhipa, Rishi, Cho, Ju Hwan, Mohyeldin, Ahmed, Beck, Samuel, Kurozumi, Kazuhiko, Kuroiwa, Toshihiko, Iwata, Ryoichi, Asai, Akio, Kim, Jonghwan, Sulman, Erik P., and Cheng, Shi-Yuan
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SERINE/THREONINE kinases , *MESENCHYMAL stem cells , *GLIOMAS , *STEM cells , *NF-kappa B - Abstract
Summary Activation of nuclear factor κB (NF-κB) induces mesenchymal (MES) transdifferentiation and radioresistance in glioma stem cells (GSCs), but molecular mechanisms for NF-κB activation in GSCs are currently unknown. Here, we report that mixed lineage kinase 4 (MLK4) is overexpressed in MES but not proneural (PN) GSCs. Silencing MLK4 suppresses self-renewal, motility, tumorigenesis, and radioresistance of MES GSCs via a loss of the MES signature. MLK4 binds and phosphorylates the NF-κB regulator IKKα, leading to activation of NF-κB signaling in GSCs. MLK4 expression is inversely correlated with patient prognosis in MES, but not PN high-grade gliomas. Collectively, our results uncover MLK4 as an upstream regulator of NF-κB signaling and a potential molecular target for the MES subtype of glioblastomas. [ABSTRACT FROM AUTHOR]
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- 2016
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13. Chordoma: current concepts, management, and future directions
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Walcott, Brian P, Nahed, Brian V, Mohyeldin, Ahmed, Coumans, Jean-Valery, Kahle, Kristopher T, and Ferreira, Manuel J
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CHORDOMA , *BONE cancer , *NOTOCHORD , *SACRUM , *CANCER radiotherapy ,SPINE cancer - Abstract
Summary: Chordoma is a rare bone cancer that is aggressive, locally invasive, and has a poor prognosis. Chordomas are thought to arise from transformed remnants of notochord and have a predilection for the axial skeleton, with the most common sites being the sacrum, skull base, and spine. The gold standard treatment for chordomas of the mobile spine and sacrum is en-bloc excision with wide margins and postoperative external-beam radiation therapy. Treatment of clival chordomas is unique from other locations with an enhanced emphasis on preservation of neurological function, typified by a general paradigm of maximally safe cytoreductive surgery and advanced radiation delivery techniques. In this Review, we highlight current standards in diagnosis, clinical management, and molecular characterisation of chordomas, and discuss current research. [ABSTRACT FROM AUTHOR]
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- 2012
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14. Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors.
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Pavlyukov, Marat S., Yu, Hai, Bastola, Soniya, Minata, Mutsuko, Shender, Victoria O., Lee, Yeri, Zhang, Suojun, Wang, Jia, Komarova, Svetlana, Wang, Jun, Yamaguchi, Shinobu, Alsheikh, Heba Allah, Shi, Junfeng, Chen, Dongquan, Mohyeldin, Ahmed, Kim, Sung-Hak, Shin, Yong Jae, Anufrieva, Ksenia, Evtushenko, Evgeniy G., and Antipova, Nadezhda V.
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APOPTOTIC bodies , *VESICLES (Cytology) , *GLIOBLASTOMA multiforme , *RNA splicing , *CELL proliferation , *SPLICEOSOMES - Abstract
Summary Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling between apoptotic and surviving cancer cells remain elusive. In this study, we demonstrate that apoptotic GBM cells paradoxically promote proliferation and therapy resistance of surviving tumor cells by secreting apoptotic extracellular vesicles (apoEVs) enriched with various components of spliceosomes. apoEVs alter RNA splicing in recipient cells, thereby promoting their therapy resistance and aggressive migratory phenotype. Mechanistically, we identified RBM11 as a representative splicing factor that is upregulated in tumors after therapy and shed in extracellular vesicles upon induction of apoptosis. Once internalized in recipient cells, exogenous RBM11 switches splicing of MDM4 and Cyclin D1 toward the expression of more oncogenic isoforms. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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