| 1. |
- An, Jiabin, et al.
(author)
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Inactivation of the CYLD Deubiquitinase by HPV E6 Mediates Hypoxia-Induced NF-kappa B Activation
- 2008
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In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 14:5, s. 394-407
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Journal article (peer-reviewed)abstract
- The biochemical mechanisms that underlie hypoxia-induced NF-kappa B activity have remained largely undefined. Here, we find that prolonged hypoxia-induced NF-kappa B activation is restricted to cancer cell lines infected with high-risk human papillomavirus (HPV) serotypes. The HPV-encoded E6 protein is necessary and sufficient for prolonged hypoxia-induced NF-kappa B activation in these systems. The molecular target of E6 in the NF-kappa B pathway is the CYLD lysine 63 (K63) deubiquitinase, a negative regulator of the NF-kappa B pathway. Specifically, hypoxia stimulates E6-mediated ubiquitination and proteasomal degradation of CYLD. Given the established role of NF-kappa B in human carcinogenesis, these findings provide a potential molecular/viral link between hypoxia and the adverse clinical outcomes observed in HPV-associated malignancies.
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| 2. |
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| 3. |
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| 4. |
- Bereshchenko, Oxana, et al.
(author)
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Hematopoietic Stem Cell Expansion Precedes the Generation of Committed Myeloid Leukemia-initiating Cells in C/EBP alpha Mutant AML
- 2009
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In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 16:5, s. 390-400
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Journal article (peer-reviewed)abstract
- We here use knockin mutagenesis in the mouse to model the spectrum of acquired CEBPA mutations in human acute myeloid leukemia. We find that C-terminal C/EBP alpha mutations increase the proliferation of long-term hematopoietic stem cells (LT-HSCs) in a cell-intrinsic manner and override normal HSC homeostasis, leading to expansion of premalignant HSCs. However, such mutations impair myeloid programming of HSCs and block myeloid lineage commitment when homozygous. In contrast, N-terminal C/EBP alpha mutations are silent with regards to HSC expansion, but allow the formation of committed myeloid progenitors, the templates for leukemia-initiating cells. The combination of N- and C-terminal C/EBP alpha mutations incorporates both features, accelerating disease development and explaining the clinical prevalence of this configuration of CEBPA mutations.
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| 5. |
- Berger, Ashton C, et al.
(author)
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A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.
- 2018
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 33:4, s. 690-705.e9
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Journal article (peer-reviewed)abstract
- We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.
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| 6. |
- Berry, Teeara, et al.
(author)
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The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma
- 2012
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 22:1, s. 117-130
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Journal article (peer-reviewed)abstract
- The ALK(F1174L) mutation is associated with intrinsic and acquired resistance to crizotinib and cosegregates with MYCN in neuroblastoma. In this study, we generated a mouse model overexpressing ALK(F1174L) in the neural crest. Compared to ALKF1174L and MYCN alone, co-expression of these two oncogenes led to the development of neuroblastomas with earlier onset, higher penetrance, and enhanced lethality. ALK(F1174L)/MYCN tumors exhibited increased MYCN dosage due to ALK(F1174L)-induced activation of the PI3K/AKT/mTOR and MAPK pathways, coupled with suppression of MYCN pro-apoptotic effects. Combined treatment with the ATP-competitive mTOR inhibitor Torin2 overcame the resistance of ALK(F1174L)/MYCN tumors to crizotinib. Our findings demonstrate a pathogenic role for ALK(F1174L) in neuroblastomas overexpressing MYCN and suggest a strategy for improving targeted therapy for ALK-positive neuroblastoma.
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| 7. |
- Best, Myron G., et al.
(author)
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RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics
- 2015
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 28:5, s. 666-676
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Journal article (peer-reviewed)abstract
- Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies".
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| 8. |
- Best, Myron G., et al.
(author)
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Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
- 2017
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In: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 32:2, s. 238-252
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Journal article (peer-reviewed)abstract
- Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.
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| 9. |
- Binder, Zev A., et al.
(author)
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Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development
- 2018
-
In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 34:1, s. 163-177
-
Journal article (peer-reviewed)abstract
- We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFR(A289D/T/V)). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR(A289D/T/V) mutants, corroborated in mice bearing intracranial tumors expressing EGFR(A289V) and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR(A289V) tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFR(A289V) mutation in glioblastoma, postulating EGFR(A289V) as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Claesson-Welsh, Lena
(author)
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Receptor Talk and Tumor Cell Walk in Glioblastoma
- 2012
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 22:1, s. 1-2
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Journal article (other academic/artistic)abstract
- In this issue of Cancer Cell, Lu et al. describe unconventional molecular interactions in glioblastoma cells that provide a mechanism for how anti-vascular endothelial growth factor therapy may promote mesenchymal transition of glioblastoma cells and increase tumor invasion.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Hedegaard, Jakob, et al.
(author)
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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
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Journal article (peer-reviewed)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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| 21. |
- Heuser, Michael, et al.
(author)
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Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex.
- 2011
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In: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 20:1, s. 39-52
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Journal article (peer-reviewed)abstract
- Pathways defining susceptibility of normal cells to oncogenic transformation may be valuable therapeutic targets. We characterized the cell of origin and its critical pathways in MN1-induced leukemias. Common myeloid (CMP) but not granulocyte-macrophage progenitors (GMP) could be transformed by MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that MN1-leukemogenicity required the MEIS1/AbdB-like HOX-protein complex. ChIP-sequencing identified common target genes of MN1 and MEIS1 and demonstrated identical binding sites for a large proportion of their chromatin targets. Transcriptional repression of MEIS1 targets in established MN1 leukemias demonstrated antileukemic activity. As MN1 relies on but cannot activate expression of MEIS1/AbdB-like HOX proteins, transcriptional activity of these genes determines cellular susceptibility to MN1-induced transformation and may represent a promising therapeutic target.
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| 22. |
- Hill, Rebecca M., et al.
(author)
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Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease
- 2015
-
In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 27:1, s. 72-84
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Journal article (peer-reviewed)abstract
- We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically.
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| 23. |
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| 24. |
- Hua, Kuo-Tai, et al.
(author)
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N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
- 2011
-
In: Cancer Cell. - : Cell Press. - 1535-6108 .- 1878-3686. ; 19:2, s. 218-231
-
Journal article (peer-reviewed)abstract
- N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.
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| 25. |
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| 26. |
- In ’t Veld, Sjors G.J.G., et al.
(author)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
-
In: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Journal article (peer-reviewed)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 27. |
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| 28. |
- Kasper, M, et al.
(author)
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Smoothing out drug resistance
- 2013
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In: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 23:1, s. 3-5
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Journal article (peer-reviewed)
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| 29. |
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| 30. |
- Kirstetter, Peggy, et al.
(author)
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Modeling of C/EBP alpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells
- 2008
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In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 13:4, s. 299-310
-
Journal article (peer-reviewed)abstract
- Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBP alpha isoform (p42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. p42-deficient leukemia could be transferred by a Mac1(+)c-Kit(+) population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1(+)c-Kit(+) progenitors revealed a signature shared with MLL-AF9-transformed AML.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Lechman, Eric R, et al.
(author)
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miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
- 2016
-
In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 29:2, s. 214-228
-
Journal article (peer-reviewed)abstract
- To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
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| 37. |
- Lee, Benjamin H., et al.
(author)
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FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia
- 2007
-
In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 12:4, s. 367-380
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Journal article (peer-reviewed)abstract
- Despite their known transforming properties, the effects of leukemogenic FLT3-ITD mutations on hematopoietic stem and multipotent progenitor cells and on hematopoietic differentiation are not well understood. We report a mouse model harboring an ITD in the murine Flt3 locus that develops myeloproliferative disease resembling CMML and further identified FLT3-ITD mutations in a subset of human CMML. These findings correlated with an increase in number, cell cycling, and survival of multipotent stem and progenitor cells in an ITD dose-dependent manner in animals that exhibited alterations within their myeloid progenitor compartments and a block in normal B cell development. This model provides insights into the consequences of constitutive signaling by an oncogenic tyrosine kinase on hematopoietic progenitor quiescence, function, and cell fate.
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| 38. |
- Lugano, Roberta, et al.
(author)
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Vascular characterization reveals immunomodulatory targets for brain metastases
- 2024
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In: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 42:3, s. 328-330
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Journal article (peer-reviewed)abstract
- Brain metastases are clinically challenging due to the unique brain microenvironment. In this issue of Cancer Cell, Bejarano et al. use transcriptional profiling and data integration to shed light on the molecular and cellular composition of the vasculature in brain metastases, identifying CD276 as an immunomodulatory target for therapy.
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| 39. |
- Ma, Jianhui, et al.
(author)
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Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair
- 2019
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 35:3, s. 504-518.e7
-
Journal article (peer-reviewed)abstract
- Ionizing radiation (IR) and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knockin mice showed radiation sensitivity. These results suggest that FGFR-mediated pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.
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| 40. |
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| 41. |
- Madsen, Chris
(author)
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Pancreatic cancer is suppressed by fibroblast-derived collagen I
- 2021
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In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 39:4, s. 451-453
-
Research review (peer-reviewed)abstract
- Clinical implementation of anti-stromal therapies in pancreatic cancer has been delayed by unanticipated tumor-restraining properties of the desmoplastic stroma. In confronting these challenges, Chen et al. demonstrate in this issue of Cancer Cell that fibroblast-specific deletion of collagen I, in the background of oncogenic Kras-induced spontaneous murine pancreatic ductal adenocarcinoma, enhances immunesuppression and accelerates progression of disease.
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| 42. |
- Mansouri, Larry, et al.
(author)
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Unraveling the DNA Methylome in Mantle Cell Lymphoma : New Insights into the Cellular Origin
- 2016
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:5, s. 665-667
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Journal article (other academic/artistic)abstract
- Our understanding of the DNA methylome and its impact on cancer evolution and disease progression is rapidly evolving. In this issue of Cancer Cell, Queiros et al. provide a detailed characterization of the DNA methylome in mantle cell lymphoma and reveal novel molecular subtypes, potentially with different cellular origins.
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| 43. |
- Mohr, Sebastian, et al.
(author)
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Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia.
- 2017
-
In: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 31:4
-
Journal article (peer-reviewed)abstract
- The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression butis currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
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| 44. |
- Mondal, Tanmoy, 1981, et al.
(author)
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Sense-antisense lncRNA pair encoded by locus 6p22.3 determines neuroblastoma susceptibility via the USP36-CHD7-SOX9 regulatory axis
- 2018
-
In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 33:3
-
Journal article (peer-reviewed)abstract
- Trait-associated loci often map to genomic regions encoding long noncoding RNAs (lncRNAs), but the role of these lncRNAs in disease etiology is largely unexplored. We show that a pair of sense/antisense lncRNA (6p22lncRNAs) encoded by CASC15 and NBAT1 located at the neuroblastoma (NB) risk-associated 6p22.3 locus are tumor suppressors and show reduced expression in high-risk NBs. Loss of functional synergy between 6p22lncRNAs results in an undifferentiated state that is maintained by a gene-regulatory network, including SOX9 located on 17q, a region frequently gained in NB. 6p22lncRNAs regulate SOX9 expression by controlling CHD7 stability via modulating the cellular localization of USP36, encoded by another 17q gene. This regulatory nexus between 6p22.3 and 17q regions may lead to potential NB treatment strategies.
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| 45. |
- Palazon, Asis, et al.
(author)
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An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression
- 2017
-
In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 32:5, s. 5-683
-
Journal article (peer-reviewed)abstract
- Cytotoxic T cells infiltrating tumors are thought to utilize HIF transcription factors during adaptation to the hypoxic tumor microenvironment. Deletion analyses of the two key HIF isoforms found that HIF-1α, but not HIF-2α, was essential for the effector state in CD8+ T cells. Furthermore, loss of HIF-1α in CD8+ T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization. Deletion of VEGF-A, an HIF target gene, in CD8+ T cells accelerated tumorigenesis while also altering vascularization. Analyses of human breast cancer showed inverse correlations between VEGF-A expression and CD8+ T cell infiltration, and a link between T cell infiltration and vascularization. These data demonstrate that the HIF-1α/VEGF-A axis is an essential aspect of tumor immunity. Palazon et al. demonstrate the importance of the HIF-1α/VEGF-A axis in tumor immunity. HIF-1α, but not HIF-2α, drives CD8+ T cell glycolytic metabolism, migration, and effector function, while the HIF-1α transcriptional target VEGF-A contributes to tumor vascularization.
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| 46. |
- Pandey, Gaurav Kumar, et al.
(author)
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The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation.
- 2014
-
In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:5, s. 722-737
-
Journal article (peer-reviewed)abstract
- Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptomes of low- and high-risk neuroblastomas, we detected differentially expressed annotated and nonannotated long noncoding RNAs (lncRNAs). We identified a lncRNA neuroblastoma associated transcript-1 (NBAT-1) as a biomarker significantly predicting clinical outcome of neuroblastoma. CpG methylation and a high-risk neuroblastoma associated SNP on chromosome 6p22 functionally contribute to NBAT-1 differential expression. Loss of NBAT-1 increases cellular proliferation and invasion. It controls these processes via epigenetic silencing of target genes. NBAT-1 loss affects neuronal differentiation through activation of the neuronal-specific transcription factor NRSF/REST. Thus, loss of NBAT-1 contributes to aggressive neuroblastoma by increasing proliferation and impairing differentiation of neuronal precursors.
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| 47. |
- Pe'er, D, et al.
(author)
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Tumor heterogeneity
- 2021
-
In: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 39:8, s. 1015-1017
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Journal article (peer-reviewed)
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| 48. |
- Persson, Anders I, et al.
(author)
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Non-stem cell origin for oligodendroglioma
- 2010
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 18:6, s. 669-682
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Journal article (peer-reviewed)abstract
- Malignant astrocytic brain tumors are among the most lethal cancers. Quiescent and therapy-resistant neural stem cell (NSC)-like cells in astrocytomas are likely to contribute to poor outcome. Malignant oligodendroglial brain tumors, in contrast, are therapy sensitive. Using magnetic resonance imaging (MRI) and detailed developmental analyses, we demonstrated that murine oligodendroglioma cells show characteristics of oligodendrocyte progenitor cells (OPCs) and are therapy sensitive, and that OPC rather than NSC markers enriched for tumor formation. MRI of human oligodendroglioma also suggested a white matter (WM) origin, with markers for OPCs rather than NSCs similarly enriching for tumor formation. Our results suggest that oligodendroglioma cells show hallmarks of OPCs, and that a progenitor rather than a NSC origin underlies improved prognosis in patients with this tumor.
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| 49. |
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| 50. |
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