Scientists demonstrated that apoptosis induced by JQ1 was solely attributed to the pro-apoptotic protein Bim. Conversely, cell-cycle regulation by JQ1 was associated with multiple Myc-associated gene targets.
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Temporal Analysis of Brd4 Displacement in the Control of B Cell Survival, Proliferation, and Differentiation: Cell Reports. (n.d.). Retrieved October 23, 2020, from https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31279-1 Cite
To discover modulators of androgen receptor (AR)-variant activity, investigtors used a lysate-based small-molecule microarray assay and identified KI-ARv-03 as an AR-variant complex binder that reduced AR-driven transcription and proliferation in prostate cancer cells.
[Cell Chemical Biology]
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Richters, A., Doyle, S. K., Freeman, D. B., Lee, C., Leifer, B. S., Jagannathan, S., Kabinger, F., Koren, J. V., Struntz, N. B., Urgiles, J., Stagg, R. A., Curtin, B. H., Chatterjee, D., Mathea, S., Mikochik, P. J., Hopkins, T. D., Gao, H., Branch, J., Xin, H., … Koehler, A. N. (2020). Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors. Cell Chemical Biology, 0(0). https://doi.org/10.1016/j.chembiol.2020.10.001 Cite
Investigators demonstrated that primary MYCHigh human small cell lung cancer tumors contain abundant guanosine nucleotides.
[Journal of Clinical Investigation]
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Huang, F., Huffman, K., Wang, Z., Wang, X., Li, K., Cai, F., Yang, C., Cai, L., Shih, T. S., Zacharias, L. G., Chung, A. S., Yang, Q., Chalishazar, M. D., Ireland, A. S., Stewart, C. A., Cargill, K. R., Girard, L., Liu, Y., Ni, M., … DeBerardinis, R. (2020). Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small cell lung cancer. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI139929 Cite
The authors demonstrated the reproducibility and stability of data from multiple sources and validate the small cell lung cancer (SCLC) consensus nomenclature on the basis of expression of master transcription factors NEUROD1, ASCL1, POU2F3, and YAP1.
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Tlemsani, C., Pongor, L., Elloumi, F., Girard, L., Huffman, K. E., Roper, N., Varma, S., Luna, A., Rajapakse, V. N., Sebastian, R., Kohn, K. W., Krushkal, J., Aladjem, M. I., Teicher, B. A., Meltzer, P. S., Reinhold, W. C., Minna, J. D., Thomas, A., & Pommier, Y. (2020). SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures. Cell Reports, 33(3). https://doi.org/10.1016/j.celrep.2020.108296 Cite
To investigate which oncogenic drivers co-operate with Zmat3 loss to promote neoplastic transformation, researchers utilized Zmat3 knockout mice in models of c-MYC-driven lymphomagenesis and KrasG12D-driven lung adenocarcinoma development.
[Cell Death & Disease]
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Scientists discuss molecular maintenance in leukemia stem cells in chronic myeloid leukemia and provide a more in-depth discussion of the dual-specificity kinase DYRK2, which has been identified as a novel actionable checkpoint in a critical leukemic network.
[Experimental and Molecular Medicine]
Scientists used patient-derived organoids derived from a familial adenomatous polyposis patient to analyze the response to chemotherapeutic agents targeting EGFR, BRAF and MEK.
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Osumi, H., Muroi, A., Sakahara, M., Kawachi, H., Okamoto, T., Natsume, Y., Yamanaka, H., Takano, H., Kusama, D., Shinozaki, E., Ooki, A., Yamaguchi, K., Ueno, M., Takeuchi, K., Noda, T., Nagayama, S., Koshikawa, N., & Yao, R. (2020). Evaluation of the RAS signaling network in response to MEK inhibition using organoids derived from a familial adenomatous polyposis patient. Scientific Reports, 10(1), 17455. https://doi.org/10.1038/s41598-020-74530-x Cite
Researchers found that decreased tyrosine-protein phosphatase nonreceptor type 13 (PTPN13) expression was associated with hepatitis B virus/hepatitis B x protein. Patients with low PTPN13 expression showed a poor prognosis. Functional assays revealed that PTPN13 inhibited proliferation and tumorigenesis in vitro and in vivo.
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Yan, Y., Huang, P., Mao, K., He, C., Xu, Q., Zhang, M., Liu, H., Zhou, Z., Zhou, Q., Zhou, Q., Ou, B., Liu, Q., Lin, J., Chen, R., Wang, J., Zhang, J., & Xiao, Z. (2020). Anti-oncogene PTPN13 inactivation by hepatitis B virus X protein counteracts IGF2BP1 to promote hepatocellular carcinoma progression. Oncogene, 1–18. https://doi.org/10.1038/s41388-020-01498-3 Cite
Investigators showed that Gfi1 augmented the expression of c-Myc protein in cells transfected with c-Myc expression constructs. The N-terminal SNAG domain and C-terminal ZF domains of Gfi1, but not its transcriptional repression and DNA binding activities, were required for c-Myc upregulation.
Scientists demonstrated for the first time, that lineage switching to neuroendocrine states was accompanied by key miRNA alterations including downregulation of miR-106a~363 cluster and upregulation of miR-301a and miR-375. They identified novel miRNA neuroendocrine differentiation drivers that can be exploited for neuroendocrine prostate cancer therapeutic targeting.
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Bhagirath, D., Liston, M., Patel, N., Akoto, T., Lui, B., Yang, T. L., To, D. M., Majid, S., Dahiya, R., Tabatabai, Z. L., & Saini, S. (2020). MicroRNA determinants of neuroendocrine differentiation in metastatic castration-resistant prostate cancer. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01493-8 Cite
On one side, JMJD3 induced the pro-senescence factor Ink4a and degraded the pluripotency regulator PHF20 in a reprogramming factor-independent manner. On the other side, JMJD3 was specifically recruited by KLF4 to reduce H3K27me3 at both enhancers and promoters of epithelial and pluripotency genes.
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Huang, Y., Zhang, H., Wang, L., Tang, C., Qin, X., Wu, X., Pan, M., Tang, Y., Yang, Z., Babarinde, I. A., Lin, R., Ji, G., Lai, Y., Xu, X., Su, J., Wen, X., Satoh, T., Ahmed, T., Malik, V., … Qin, B. (2020). JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency. Nature Communications, 11(1), 5061. https://doi.org/10.1038/s41467-020-18900-z Cite