Scientists found that the CCAAT/Enhancer-binding protein delta (CEBPD) protein levels in glioblastoma patients were significantly increased and further contributed to temozolamide resistance by promoting glioma-like stem cell formation.
[Cell Death Discovery]
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Wang, S.-M., Lin, W.-C., Lin, H.-Y., Chen, Y.-L., Ko, C.-Y., & Wang, J.-M. (2021). CCAAT/Enhancer-binding protein delta mediates glioma stem-like cell enrichment and ATP-binding cassette transporter ABCA1 activation for temozolomide resistance in glioblastoma. Cell Death Discovery, 7(1), 1–11. https://doi.org/10.1038/s41420-020-00399-4 Cite
Researchers observed that treatment of melanoma cells with the B-Raf Proto-Oncogene, Serine/Threonine Kinase inhibitor vemurafenib caused an increased cell surface expression and activation of human epidermal growth factor receptor 3 (HER3) by shed ligands
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Hüser, L., Kokkaleniou, M.-M., Granados, K., Dworacek, J., Federico, A., Vierthaler, M., Novak, D., Arkhypov, I., Hielscher, T., Umansky, V., Altevogt, P., & Utikal, J. (2020). HER3-Receptor-Mediated STAT3 Activation Plays a Central Role in Adaptive Resistance toward Vemurafenib in Melanoma. Cancers, 12(12), 3761. https://doi.org/10.3390/cancers12123761 Cite
Using mouse models of skin squamous cell carcinoma and lung tumors, investigators found that deletion of Fat1 accelerated tumour initiation and malignant progression and promoted a hybrid epithelial-to-mesenchymal transition (EMT) phenotype.
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Pastushenko, I., Mauri, F., Song, Y., de Cock, F., Meeusen, B., Swedlund, B., Impens, F., Van Haver, D., Opitz, M., Thery, M., Bareche, Y., Lapouge, G., Vermeersch, M., Van Eycke, Y.-R., Balsat, C., Decaestecker, C., Sokolow, Y., Hassid, S., Perez-Bustillo, A., … Blanpain, C. (2020). Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis. Nature, 1–8. https://doi.org/10.1038/s41586-020-03046-1 Cite
Using an RNA-seq platform, scientists identified and validated the differential gene expression of five transcription factors that were associated with a remarkable increase in the number of iPSC colonies generated from a patient with Parkinson’s disease.
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Swaidan, N. T., Salloum-Asfar, S., Palangi, F., Errafii, K., Soliman, N. H., Aboughalia, A. T., Wali, A. H. S., Abdulla, S. A., & Emara, M. M. (2020). Identification of potential transcription factors that enhance human iPSC generation. Scientific Reports, 10(1), 21950. https://doi.org/10.1038/s41598-020-78932-9 Cite
Overexpression of stemness factors NANOG, OCT4 and SOX2 by introduction of gene constructs in Hep3B cells suppressed two miRNA expression levels. Treatment of chromeceptin, an IGF signaling pathway inhibitor, decreased numbers of tumorsphere and inhibited the AKT/mTOR pathway.
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The correlation of expression of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) and clinical features and gastric cancer patients’ outcomes was evaluated. Knockdown or exogenous expression of TBL1XR1 was combined with in vitro and in vivo assays to evaluate the function of TBL1XR1.
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Lu, J., Bang, H., Kim, S. M., Cho, S.-J., Ashktorab, H., Smoot, D. T., Zheng, C., Ryeom, S. W., Yoon, S. S., Yoon, C., & Lee, J. H. (2020). Lymphatic metastasis-related TBL1XR1 enhances stemness and metastasis in gastric cancer stem-like cells by activating ERK1/2-SOX2 signaling. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01571-x Cite
Investigators showed that the upregulation of SOX2 was central to cancer-associated fibroblasts (CAFs) promoting tumor malignancy, which was repressed by protein kinase Cζ (PKCζ). PKCζ deficiency activated the reprogramming of colonic fibroblasts to generate a predominant SOX2-dependent CAF population expressing the WNT regulator Sfrp2 as its top biomarker.
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Kasashima, H., Duran, A., Martinez-Ordoñez, A., Nakanishi, Y., Kinoshita, H., Linares, J. F., Reina-Campos, M., Kudo, Y., L’Hermitte, A., Yashiro, M., Ohira, M., Bao, F., Tauriello, D. V. F., Batlle, E., Diaz-Meco, M. T., & Moscat, J. (2020). Stromal SOX2 Upregulation Promotes Tumorigenesis through the Generation of a SFRP1/2-Expressing Cancer-Associated Fibroblast Population. Developmental Cell, 0(0). https://doi.org/10.1016/j.devcel.2020.10.014 Cite
One promising alternative can be human pluripotent stem cells (PSCs) that provide an unlimited source of cells. Human PSCs, including embryonic stem cells and induced pluripotent stem cells, are self-renewing progenitors that can be differentiated to lineages of ectoderm, mesoderm, and endoderm.
[Stem Cell Research & Therapy]
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Investigators report a mechanism regulated by the oncogenic SOX2-GLI1 transcriptional complex driving melanoma invasion through the induction of the sialyltransferase ST3GAL1. Using in vitro and in vivo studies, they demonstrated that ST3GAL1 drove melanoma metastasis.
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Pietrobono, S., Anichini, G., Sala, C., Manetti, F., Almada, L. L., Pepe, S., Carr, R. M., Paradise, B. D., Sarkaria, J. N., Davila, J. I., Tofani, L., Battisti, I., Arrigoni, G., Ying, L., Zhang, C., Li, H., Meves, A., Fernandez-Zapico, M. E., & Stecca, B. (2020). ST3GAL1 is a target of the SOX2-GLI1 transcriptional complex and promotes melanoma metastasis through AXL. Nature Communications, 11(1), 5865. https://doi.org/10.1038/s41467-020-19575-2 Cite
Deregulation of PARK7 has been implicated in the pathogenesis of various human diseases, including cancer. Scientists clarified the effect of PARK7 on stemness and radioresistance of glioblastoma stem cells.
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Investigators first defined the transcription factors (TF) reprogramome, i.e., the full complement of TFs to be reprogrammed. Most TFs were resistant to OCT4, SOX2, KLF4, and MYC reprogramming at the initial stages, an observation consistent with the inefficiency and long latency of iPSC reprogramming.
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Cevallos, R. R., Edwards, Y. J. K., Parant, J. M., Yoder, B. K., & Hu, K. (2020). Human transcription factors responsive to initial reprogramming predominantly undergo legitimate reprogramming during fibroblast conversion to iPSCs. Scientific Reports, 10(1), 19710. https://doi.org/10.1038/s41598-020-76705-y Cite