Distinct Functions of Transforming Growth Factor-β Signaling in C-MYC Driven Hepatocellular Carcinoma Initiation and Progression

Scientists investigated the expression of TGFβ signaling in c-MYC amplified human hepatocellular carcinoma samples as well as the mechanisms whereby TGFβ modulated c-Myc driven hepatocarcinogenesis during initiation and progression.
[Cell Death & Disease]
Wang, H., Wang, P., Xu, M., Song, X., Wu, H., Evert, M., Calvisi, D. F., Zeng, Y., & Chen, X. (2021). Distinct functions of transforming growth factor-β signaling in c-MYC driven hepatocellular carcinoma initiation and progression. Cell Death & Disease, 12(2), 1–16. https://doi.org/10.1038/s41419-021-03488-z Cite
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The miR-200c/141-ZEB2-TGFβ Axis Is Aberrant in Human T-Cell Prolymphocytic Leukemia

Researchers revealed that the expression of miRNAs was aberrant and often heterogeneous in T cell prolymphocytic leukemia (T-PLL). They identified 35 miRNAs that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster.
[Haematologica]
Erkeland, S. J., Stavast, C. J., Schilperoord-Vermeulen, J., Collo, G. D., Werken, H. J. G. van de, Leon, L. G., Hoven-Beijen, A. van, Zuijen, I. van, Mueller, Y. M., Bindels, E. M., Ridder, D. de, Kappers-Klunne, M. C., Lom, K. van, Velden, V. H. J. van der, & Langerak, A. W. (2020). The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia. Haematologica. https://doi.org/10.3324/haematol.2020.263756 Cite
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Crenolanib Regulates ERk and AKT/mTOR Signaling Pathways in RAS/BRAF-Mutated Colorectal Cancer Cells and Organoids

Scientists used multiple colorectal cancer (CRC) cell lines to investigate the growth-inhibitory effect of crenolanib and its effect in combination with other cytotoxic agents. Primary cultures of patient-derived organoids, a model that reflects the heterogeneity of clinical CRC, were used to further validate the effects of crenolanib.
[Molecular Cancer Research]
Fujino, S., Miyoshi, N., Ito, A., Yasui, M., Ohue, M., Ogino, T., Takahashi, H., Uemura, M., Matsuda, C., Mizushima, T., Doki, Y., & Eguchi, H. (2021). Crenolanib regulates ERK and AKT/mTOR signaling pathways in RAS/BRAF-mutated colorectal cancer cells and organoids. Molecular Cancer Research. https://doi.org/10.1158/1541-7786.MCR-20-0600 Cite
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TGFβ Signaling Curbs Cell Fusion and Muscle Regeneration

Investigators showed that transforming growth factor beta (TGFβ) pathway was active in adult muscle cells throughout fusion. They found TGFβ signaling reduced cell fusion, regardless of the cells’ ability to move and establish cell-cell contacts.
[Nature Communications]
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TGFβ Signaling Acts as a Molecular Brake of Myoblast Fusion

Researchers uncovered, through high-throughput in vitro assays and in vivo studies in the chicken embryo, that TGFβ signaling acts specifically and uniquely as a molecular brake on muscle fusion.
[Nature Communications]
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Immune Dysfunction in Developmental Programming of Type 2 Diabetes Mellitus

Several activated immune pathways have been identified in the islets of people who experienced itrauterine growth restriction, with alternations in the levels of IL-1β and IL-4 as well as changes in TGFβ signaling. Leptin levels are also altered.
[Nature Reviews Endocrinology]
Golden, T. N., & Simmons, R. A. (2021). Immune dysfunction in developmental programming of type 2 diabetes mellitus. Nature Reviews Endocrinology, 1–11. https://doi.org/10.1038/s41574-020-00464-z Cite
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MicroRNA-331 Inhibits Isoproterenol-Induced Expression of Profibrotic Genes in Cardiac Myofibroblasts via the TGFβ/smad3 Signaling Pathway

Scientists provided evidence to prove that the fibrosis process could be regulated by miR-331 through targeting TGFβ signaling.
[Scientific Reports]
Yousefi, F., Soltani, B. M., & Rabbani, S. (2021). MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway. Scientific Reports, 11(1), 2548. https://doi.org/10.1038/s41598-021-82226-z Cite
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AIM2 in Regulatory T Cells Restrains Autoimmune Diseases

Scientists showed that the DNA-binding inflammasome receptor AIM2 had a T cell-intrinsic and inflammasome-independent role in the function of T regulatory cells.
[Nature]
Chou, W.-C., Guo, Z., Guo, H., Chen, L., Zhang, G., Liang, K., Xie, L., Tan, X., Gibson, S. A., Rampanelli, E., Wang, Y., Montgomery, S. A., Brickey, W. J., Deng, M., Freeman, L., Zhang, S., Su, M. A., Chen, X., Wan, Y. Y., & Ting, J. P.-Y. (2021). AIM2 in regulatory T cells restrains autoimmune diseases. Nature, 1–6. https://doi.org/10.1038/s41586-021-03231-w Cite
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EEF1A2 Interacts with HSP90AB1 to Promote Lung Adenocarcinoma Metastasis via Enhancing TGF-β/SMAD Signaling

Scientists report that eukaryotic protein translation elongation factor 1α2 (EEF1A2) mediates the epithelial–mesenchymal transformation, to promote the metastasis of lung adenocarcinoma cells in vitro and in vivo.
[British Journal of Cancer]
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Cytotoxic T Cells Isolated from Healthy Donors and Cancer Patients Kill TGFβ-Expressing Cancer Cells in a TGFβ-Dependent Manner

Investigators showed that healthy donors and cancer patients harbor CD4+ and CD8+ T cells specific for TGFβ-derived epitopes and that cytotoxic T cells with specificity toward TGFβ-derived epitopes were able to recognize and kill cancer cell lines in a TGFβ-dependent manner.
[Cellular & Molecular Immunology]
Holmström, M. O., Mortensen, R. E. J., Pavlidis, A. M., Martinenaite, E., Weis-Banke, S. E., Aaboe-Jørgensen, M., Bendtsen, S. K., Met, Ö., Pedersen, A. W., Donia, M., Svane, I. M., & Andersen, M. H. (2021). Cytotoxic T cells isolated from healthy donors and cancer patients kill TGFβ-expressing cancer cells in a TGFβ-dependent manner. Cellular & Molecular Immunology, 1–12. https://doi.org/10.1038/s41423-020-00593-5 Cite
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Integrin αvβ6–TGFβ–SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer

The authors identified the SOX4 transcription factor as an important resistance mechanism to T cell-mediated cytotoxicity for TNBC cells
[Cancer Cell]
Bagati, A., Kumar, S., Jiang, P., Pyrdol, J., Zou, A. E., Godicelj, A., Mathewson, N. D., Cartwright, A. N. R., Cejas, P., Brown, M., Giobbie-Hurder, A., Dillon, D., Agudo, J., Mittendorf, E. A., Liu, X. S., & Wucherpfennig, K. W. (2020). Integrin αvβ6–TGFβ–SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2020.12.001 Cite
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