Gli1+ Mesenchymal Stromal Cells Form a Pathological Niche to Promote Airway Progenitor Metaplasia in the Fibrotic Lung

Scientists showed that Gli1+ MSCs, previously shown to contribute to myofibroblasts during scarring, promoted metaplastic differentiation of airway progenitors into KRT5+ basal cells.
[Nature Cell Biology]
Cassandras, M., Wang, C., Kathiriya, J., Tsukui, T., Matatia, P., Matthay, M., Wolters, P., Molofsky, A., Sheppard, D., Chapman, H., & Peng, T. (2020). Gli1 + mesenchymal stromal cells form a pathological niche to promote airway progenitor metaplasia in the fibrotic lung. Nature Cell Biology, 1–12. https://doi.org/10.1038/s41556-020-00591-9 Cite
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AP-1 and TGFß Cooperativity Drives Non-Canonical Hedgehog Signaling in Resistant Basal Cell Carcinoma

The authors used single cell RNA-sequencing of patient tumors to identify three prognostic surface markers (LYPD3, TACSTD2, and LY6D) which correlated with myocardin-related transcription factor (nMRTF) and resistance to Smoothened inhibitors. The nMRTF cell state resembled transit-amplifying cells of the hair follicle matrix, with AP-1 and TGFß cooperativity driving nMRTF activation.
[Nature Communications]
Yao, C. D., Haensel, D., Gaddam, S., Patel, T., Atwood, S. X., Sarin, K. Y., Whitson, R. J., McKellar, S., Shankar, G., Aasi, S., Rieger, K., & Oro, A. E. (2020). AP-1 and TGFß cooperativity drives non-canonical Hedgehog signaling in resistant basal cell carcinoma. Nature Communications, 11(1), 5079. https://doi.org/10.1038/s41467-020-18762-5 Cite
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Transient Activation of the Hedgehog-Gli Pathway Rescues Radiotherapy-Induced Dry Mouth via Recovering Salivary Gland Resident Macrophages

Researchers showed in mice that activation of canonical Gli-dependent Hedgehog signaling by Gli1 gene transfer was sufficient to recover salivary function impaired by irradiation.
[Cancer Research]
Zhao, Q., Zhang, L., Hai, B., Wang, J., Baetge, C. L., Deveau, M. A., Kapler, G. M., Feng, J. Q., & Liu, F. (2020). Transient activation of the Hedgehog-Gli pathway rescues radiotherapy-induced dry mouth via recovering salivary gland resident macrophages. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-0503 Cite
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Berberine Inhibits Colorectal Tumor Growth by Suppressing SHH Secretion

Berberine promotes the degradation of SHH mRNA in colorectal cancer cells, interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth.
[Acta Pharmacologica Sinica]
Berberine inhibits colorectal tumor growth by suppressing SHH secretion | Acta Pharmacologica Sinica. (n.d.). Retrieved September 21, 2020, from https://www.nature.com/articles/s41401-020-00514-2 Cite
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Combined Inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 Pathways Suppresses Breast Cancer Stem Cells, Tumor Growth, and Metastasis

Investigators showed that novel combinations of JAK2 inhibitors with SMO inhibitors synergistically inhibited in vitro growth of TNBC and HER2-positive trastuzumab-resistant BT474-TtzmR cells.
[Oncogene]
Doheny, D., Sirkisoon, S., Carpenter, R. L., Aguayo, N. R., Regua, A. T., Anguelov, M., Manore, S. G., Arrigo, A., Jalboush, S. A., Wong, G. L., Yu, Y., Wagner, C. J., Chan, M., Ruiz, J., Thomas, A., Strowd, R., Lin, J., & Lo, H.-W. (2020). Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways suppresses breast cancer stem cells, tumor growth, and metastasis. Oncogene, 1–17. https://doi.org/10.1038/s41388-020-01454-1 Cite
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Crosstalk Between Hedgehog Pathway and the Glucocorticoid Receptor Pathway as a Basis for Combination Therapy in T-Cell Acute Lymphoblastic Leukemia

Researchers presented a therapeutically relevant crosstalk between Hedgehog (HH) signaling and the glucocorticoid receptor pathway acting at the level of GLI1 transcription factor.
[Oncogene]
Bongiovanni, D., Tosello, V., Saccomani, V., Dalla Santa, S., Amadori, A., Zanovello, P., & Piovan, E. (2020). Crosstalk between Hedgehog pathway and the glucocorticoid receptor pathway as a basis for combination therapy in T-cell acute lymphoblastic leukemia. Oncogene, 1–12. https://doi.org/10.1038/s41388-020-01453-2 Cite
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LIN28B-AS1-IGF2BP1 Binding Promotes Hepatocellular Carcinoma Cell Progression

The authors showed that LIN28B-AS1 was expressed in established/primary human hepatocellular carcinoma (HCC) cells and HCC tissues. RNA-immunoprecipitation and RNA pull-down results confirmed that LIN28B-AS1 directly associated with IGF2BP1 protein in HCC cells.
[Cell Death & Disease]
Zhang, J., Hu, K., Yang, Y., Wang, Y., Zheng, Y., Jin, Y., Li, P., & Cheng, L. (2020). LIN28B-AS1-IGF2BP1 binding promotes hepatocellular carcinoma cell progression. Cell Death & Disease, 11(9), 1–12. https://doi.org/10.1038/s41419-020-02967-z Cite
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Hedgehog Signaling Enables Repair of Ribosomal DNA Double-Strand Breaks

Investigators found that glioma-associated oncogene family zinc finger 1was activated in TNBC cells in response to ionizing radiation (IR) and localized to ribosomal DNA (rDNA) sequences in response to both global double-strand breaks (DSBs) generated by IR and site-specific DSBs in rDNA.
[Nucleic Acids Research]
Lama-Sherpa, T. D., Lin, V. T. G., Metge, B. J., Weeks, S. E., Chen, D., Samant, R. S., & Shevde, L. A. (n.d.). Hedgehog signaling enables repair of ribosomal DNA double-strand breaks. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa733 Cite
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Garcinone C Suppresses Colon Tumorigenesis through the Gli1-dependent Hedgehog Signaling Pathway

Colony formation assay and flow cytometry were used to evaluate the effect of garcinone C on the proliferation and cell cycle progression of colon cancer cells.
[Phytomedicine]
Chen, J., Qiu, S., Kim, J. T., Cho, J. S., Moon, J. H., Zhou, Y., Auh, J.-H., & Lee, H. J. (2020). Garcinone C Suppresses Colon Tumorigenesis Through the Gli1-dependent Hedgehog Signaling Pathway. Phytomedicine, 153334. https://doi.org/10.1016/j.phymed.2020.153334 Cite
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Tumour Suppressor 15-Hydroxyprostaglandin Dehydrogenase Induces Differentiation in Colon Cancer via GLI1 Inhibition

Scientists elucidated the mechanism by which leukotriene C4 (LTC4) – induced 15-hydroxyprostaglandin dehydrogenase (15-PGDH) promotes differentiation in colon cancer cells through cysteinyl leukotriene receptor 2 activation with the involvement of Hedgehog–GLI signalling. They observed that GLI1 was involved in the regulation of the redifferentiation and reduction in stemness induced by LTC4 via 15-PGDH in colon cancer cells.
[Oncogenesis]
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Hedgehog-GLI Signalling Promotes Chemoresistance through the Regulation of ABC Transporters in Colorectal Cancer Cells

The authors identified potential GLI1 binding sites in the promoter region of six ABC transporters. Next, they investigated the binding of GLI1 using chromatin immunoprecipitation experiments and demonstrated that GLI1 transcriptionally regulated the identified ABC transporters. This research showed that chemoresistant cells express high levels of GLI1 and of the ABC transporters and that GLI1 inhibition disrupts the transporters up-regulation.
[Scientific Reports]
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