A Massively Parallel Fluorescence Assay to Characterize the Effects of Synonymous Mutations on TP53 Expression
In this reporter context, several mutations within the exon caused strong expression changes including mutations that may cause potential gain or loss of function. Further analysis indicates that these effects are largely attributed to errors in splicing, including exon skipping, intron inclusion, and exon truncation, resulting from mutations both at exon–intron junctions and within the body of the exon. These mutations are found at extremely low frequencies in healthy populations and are enriched a few-fold in cancer genomes, suggesting that some of them may be driver mutations in TP53. This assay provides a general...
Source: Molecular Cancer Research - October 1, 2017 Category: Cancer & Oncology Authors: Bhagavatula, G., Rich, M. S., Young, D. L., Marin, M., Fields, S. Tags: Rapid Impact Source Type: research
Highlights of This Issue
(Source: Molecular Cancer Research)
Source: Molecular Cancer Research - October 1, 2017 Category: Cancer & Oncology Tags: Highlights Source Type: research
Augmented TME O-GlcNAcylation Promotes Tumor Proliferation through the Inhibition of p38 MAPK
O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. However, the role of O-GlcNAcylation in the tumor microenvironment (TME) is not fully elucidated. Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME ...
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Moriwaki, K., Asahi, M. Tags: Signal Transduction Source Type: research
MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation
This study demonstrates that the interaction occurring between MELK and EZH2 promotes self-proliferation and stemness, thus representing an attractive therapeutic target and potential candidate for diagnosis of medulloblastoma. Mol Cancer Res; 15(9); 1275–86. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Liu, H., Sun, Q., Sun, Y., Zhang, J., Yuan, H., Pang, S., Qi, X., Wang, H., Zhang, M., Zhang, H., Yu, C., Gu, C. Tags: Signal Transduction Source Type: research
KITD816V Induces SRC-Mediated Tyrosine Phosphorylation of MITF and Altered Transcription Program in Melanoma
This study demonstrates that an oncogenic tyrosine kinase mutant, KITD816V, can alter the transcriptional program of the transcription factor MITF in melanoma Mol Cancer Res; 15(9); 1265–74. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Phung, B., Kazi, J. U., Lundby, A., Bergsteinsdottir, K., Sun, J., Goding, C. R., Jönsson, G., Olsen, J. V., Steingrimsson, E., Rönnstrand, L. Tags: Oncogenes and Tumor Suppressors Source Type: research
IKK{beta}-Mediated Resistance to Skin Cancer Development Is Ink4a/Arf-Dependent
IKKβ (encoded by IKBKB) is a protein kinase that regulates the activity of numerous proteins important in several signaling pathways, such as the NF-B pathway. IKKβ exerts a protumorigenic role in several animal models of lung, hepatic, intestinal, and oral cancer. In addition, genomic and proteomic studies of human tumors also indicate that IKBKB gene is amplified or overexpressed in multiple tumor types. Here, the relevance of IKKβ in skin cancer was determined by performing carcinogenesis studies in animal models overexpressing IKKβ in the basal skin layer. IKKβ overexpression resulted in a stri...
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Page, A., Bravo, A., Suarez-Cabrera, C., Alameda, J. P., Casanova, M. L., Lorz, C., Segrelles, C., Segovia, J. C., Paramio, J. M., Navarro, M., Ramirez, A. Tags: Oncogenes and Tumor Suppressors Source Type: research
Histone H3.3K27M Represses p16 to Accelerate Gliomagenesis in a Murine Model of DIPG
This study shows that H3.3K27M mutation and PDGF signaling act in concert to accelerate gliomagenesis in a genetic mouse model and identifies repression of p16 tumor suppressor as a target of H3.3K27M, highlighting the G1–S cell-cycle transition as a promising therapeutic avenue. Mol Cancer Res; 15(9); 1243–54. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Cordero, F. J., Huang, Z., Grenier, C., He, X., Hu, G., McLendon, R. E., Murphy, S. K., Hashizume, R., Becher, O. J. Tags: Oncogenes and Tumor Suppressors Source Type: research
PPAR{delta} Reprograms Glutamine Metabolism in Sorafenib-Resistant HCC
This study provides novel insight into the mechanism underlying sorafenib resistance and a potential therapeutic strategy targeting PPAR in advanced hepatocellular carcinoma. Mol Cancer Res; 15(9); 1230–42. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Kim, M.-J., Choi, Y.-K., Park, S. Y., Jang, S. Y., Lee, J. Y., Ham, H. J., Kim, B.-G., Jeon, H.-J., Kim, J.-H., Kim, J.-G., Lee, I.-K., Park, K.-G. Tags: Metabolism Source Type: research
Real-Time Transferrin-Based PET Detects MYC-Positive Prostate Cancer
Noninvasive biomarkers that detect the activity of important oncogenic drivers could significantly improve cancer diagnosis and management of treatment. The goal of this study was to determine whether 68Ga-citrate (which avidly binds to circulating transferrin) can detect MYC-positive prostate cancer tumors, as the transferrin receptor is a direct MYC target gene. PET imaging paired with 68Ga-citrate and molecular analysis of preclinical models, human cell-free DNA (cfDNA), and clinical biopsies were conducted to determine whether 68Ga-citrate can detect MYC-positive prostate cancer. Importantly, 68Ga-citrate detected huma...
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Aggarwal, R., Behr, S. C., Paris, P. L., Truillet, C., Parker, M. F. L., Huynh, L. T., Wei, J., Hann, B., Youngren, J., Huang, J., Premasekharan, G., Ranatunga, N., Chang, E., Gao, K. T., Ryan, C. J., Small, E. J., Evans, M. J. Tags: Metabolism Source Type: research
The Landscape of Isoform Switches in Human Cancers
This study indicates that isoform switches with predicted functional consequences are common and important in dysfunctional cells, which in turn means that gene expression should be analyzed at the isoform level. Mol Cancer Res; 15(9); 1206–20. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Vitting-Seerup, K., Sandelin, A. Tags: Genomics Source Type: research
Normal and Cancerous Tissues Release Extrachromosomal Circular DNA (eccDNA) into the Circulation
Cell-free circulating linear DNA is being explored for noninvasive diagnosis and management of tumors and fetuses, the so-called liquid biopsy. Previously, we observed the presence of small extrachromosomal circular DNA (eccDNA), called microDNA, in the nuclei of mammalian tissues and cell lines. Now, we demonstrate that cell-free microDNA derived from uniquely mapping regions of the genome is detectable in plasma and serum from both mice and humans and that they are significantly longer (30%–60% >250 bases) than cell-free circulating linear DNA (~150 bases). Tumor-derived human microDNA is detected in the mouse c...
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Kumar, P., Dillon, L. W., Shibata, Y., Jazaeri, A. A., Jones, D. R., Dutta, A. Tags: Genomics Source Type: research
NR4A2 Promotes DNA Double-strand Break Repair Upon Exposure to UVR
Exposure of melanocytes to ultraviolet radiation (UVR) induces the formation of UV lesions that can produce deleterious effects in genomic DNA. Encounters of replication forks with unrepaired UV lesions can lead to several complex phenomena, such as the formation of DNA double-strand breaks (DSBs). The NR4A family of nuclear receptors are transcription factors that have been associated with mediating DNA repair functions downstream of the MC1R signaling pathway in melanocytes. In particular, emerging evidence shows that upon DNA damage, the NR4A2 receptor can translocate to sites of UV lesion by mechanisms requiring post-t...
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Yin, K., Chhabra, Y., Tropee, R., Lim, Y. C., Fane, M., Dray, E., Sturm, R. A., Smith, A. G. Tags: DNA Damage and Repair Source Type: research
Notch Represses Transcription by PRC2 Recruitment to the Ternary Complex
This study provides rationale for the targeting of epigenetic enzymes to inhibit Notch activity or use in combinatorial therapy to provide a more profound therapeutic response. Mol Cancer Res; 15(9); 1173–83. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Han, X., Ranganathan, P., Tzimas, C., Weaver, K. L., Jin, K., Astudillo, L., Zhou, W., Zhu, X., Li, B., Robbins, D. J., Capobianco, A. J. Tags: Chromatin, Epigenetics, and RNA Regulation Source Type: research
Inhibition of the Cell Death Pathway in Nonalcoholic Steatohepatitis (NASH)-Related Hepatocarcinogenesis Is Associated with Histone H4 lysine 16 Deacetylation
Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers, and its incidence is steadily increasing worldwide. Recent epidemiologic findings have suggested that the increased incidence of HCC is associated with obesity, type II diabetes mellitus, and nonalcoholic steatohepatitis (NASH); however, the mechanisms and the molecular pathogenesis of NASH-related HCC are not fully understood. To elucidate the underlying mechanisms of the development of NASH-related HCC, we investigated the hepatic transcriptomic and histone modification profiles in Stelic Animal Model mice, the first animal model of NASH-related ...
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: de Conti, A., Dreval, K., Tryndyak, V., Orisakwe, O. E., Ross, S. A., Beland, F. A., Pogribny, I. P. Tags: Chromatin, Epigenetics, and RNA Regulation Source Type: research
Near-Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody
In conclusion, the anti-PSMA antibody is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with the anti-PSMA-IR700 antibody is a promising candidate of the treatment of PSMA-expressing tumors and could be readily translated to humans.
Implications: NIR-infrared photoimmunotherapy (NIR-PIT) using a fully human anti-PSMA-IR700 conjugate showed potential therapeutic effects against a PSMA-expressing prostate cancer that is readily translated to humans. Mol Cancer Res; 15(9); 1153–62. ©2017 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - August 31, 2017 Category: Cancer & Oncology Authors: Nagaya, T., Nakamura, Y., Okuyama, S., Ogata, F., Maruoka, Y., Choyke, P. L., Kobayashi, H. Tags: Cell Death and Survival Source Type: research
