Article
Biochemistry & Molecular Biology
Ana Dunatov Huljev, Nela Kelam, Benjamin Benzon, Violeta Soljic, Natalija Filipovic, Valdi Pesutic Pisac, Merica Glavina Durdov, Katarina Vukojevic
Summary: Clear cell renal cell carcinoma (ccRCC) is the deadliest neoplasm of the urinary tract. The expression of Sonic Hedgehog (SHH) was found to be higher in grade 1 tumors and decreased with tumor progression. PTCH expression was lower in grades 1 and 2 compared to the control and grade 4, while SMO expression was higher in grade 4 than in other grades and the control. High PTCH and low SMO expression were associated with better survival rates in ccRCC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Developmental Biology
Wenguang Yin, Andreas Liontos, Janine Koepke, Maroua Ghoul, Luciana Mazzocchi, Xinyuan Liu, Chunyan Lu, Haoyu Wu, Athanasios Fysikopoulos, Alexandros Sountoulidis, Werner Seeger, Clemens Ruppert, Andreas Gunther, Didier Y. R. Stainier, Christos Samakovlis
Summary: The tracheal epithelium is a crucial element in pulmonary diseases, and its understanding of cell proliferation and differentiation is limited. The Hedgehog (HH) signaling pathway plays a role in communication between epithelial and mesenchymal cells in the lung, affecting stromal cell proliferation, differentiation, and epithelial signaling. This study discovered an autocrine HH signaling function in airway epithelial cells, with its inhibition leading to defects in cell proliferation and differentiation. Additionally, HH function is mediated by transcriptional activation, as inhibition of HH signaling downregulates cell type-specific transcription factor genes in both mouse trachea and human airway epithelial cells. These findings provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.
Article
Oncology
Liangping Yuan, Hongying Zhang, Jingbo Liu, Anshu Malhotra, Abhinav Dey, Bing Yu, Kishore Kumar Jella, Leon F. McSwain, Matthew J. Schniederjan, Tobey J. MacDonald
Summary: This study highlights the critical role of STAT3 in Shh MB cells, its essential role in Smo-dependent Shh signaling and drug resistance, and its potential as a therapeutic target to overcome anti-Smo drug resistance in treating Shh MB. Additionally, STAT3 inhibitor treatment significantly prevents tumor formation and synergistic effects with Smo inhibitors in vitro suggest a promising approach for Shh MB treatment.
MOLECULAR ONCOLOGY
(2022)
Article
Biology
Maia Kinnebrew, Giovanni Luchetti, Ria Sircar, Sara Frigui, Lucrezia Vittoria Viti, Tomoki Naito, Francis Beckert, Yasunori Saheki, Christian Siebold, Arun Radhakrishnan, Rajat Rohatgi
Summary: The study reveals that PTCH1 inhibits the activity of Smoothened by depleting accessible cholesterol from the outer leaflet of the plasma membrane, potentially involving an exchange of potassium ions. This finding establishes a general framework for investigating how proteins change cholesterol accessibility to regulate membrane-dependent processes in cells.
Review
Cell Biology
Wanchen Wang, Ryo Shiraishi, Daisuke Kawauchi
Summary: The sonic hedgehog (SHH) pathway plays a crucial role in regulating the development of the central nervous system in vertebrates, and aberrant regulation can lead to neurodevelopmental diseases and brain tumors. Research on the mechanisms of SHH in the cerebellum has shed light on structural abnormalities and medulloblastoma, with current clinical trials exploring novel therapeutic approaches.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Andres Vicente-Acosta, Alfredo Gimenez-Cassina, Javier Diaz-Nido, Frida Loria
Summary: This study found that pharmacological activation of the SHH pathway can modulate the interaction between astrocytes and neurons to prevent neurodegeneration in Friedreich's ataxia.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Huanxian Wu, Lishun Zhang, Boyu Chen, Baofang Ou, Jiahuan Xu, Nannan Tian, Danni Yang, Yangcheng Ai, Qianqing Chen, Dongling Quan, Tingting Zhang, Lin Lv, Yuanxin Tian, Jiajie Zhang, Shaoyu Wu
Summary: B13 is an effective drug that inhibits the proliferation and metastasis of colorectal cancer cells, inducing cell cycle arrest and apoptosis. It has low toxicity and superior antitumor activity compared to Vismodegib. By binding to Smo protein, B13 inhibits the expression of downstream gene Gli1 and its localization in the nucleus, overcoming resistance caused by SmoD473H mutations.
BIOORGANIC CHEMISTRY
(2023)
Article
Pediatrics
Haibao Zhang, Shan Xu, Dalin He, Xinyang Wang, Guodong Zhu
Summary: Autocrine SHH signaling was found in the developing urothelium, while paracrine SHH signaling was found in the developing smooth muscle layer, mediated by SMO, PTC-1, and GLI1 during human bladder development. The expression of SHH signaling components peaked at 12- and 23-weeks gestation, corresponding to different stages of urothelium and smooth muscle layer differentiation and development in the fetal bladder.
FRONTIERS IN PEDIATRICS
(2021)
Article
Immunology
Diana C. Yanez, Eleftheria Papaioannou, Mira M. Chawda, Jasmine Rowell, Susan Ross, Ching-In Lau, Tessa Crompton
Summary: Pharmacological inhibition of smoothened reduces Th2 cell infiltration and alleviates the severity of allergic asthma by decreasing the induction of Shh, IL-4, and IL-13, as well as lowering serum IgE levels and expression of inflammation-related genes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Nitin K. Agarwal, Chae-Hwa Kim, Kranthi Kunkalla, Amineh Vaghefi, Sandra Sanchez, Samantha Manuel, Daniel Bilbao, Francisco Vega, Ralf Landgraf
Summary: The loss of Smoothened receptor leads to preferential degradation of IGF1R over recycling and impacts AKT/PI3K signaling in cancer cells, while MAPK signaling remains unaffected. Smo plays a role in maintaining IGF1R levels and associated AKT activation in cancer cells, independent of canonical signaling. This novel function of Smoothened contributes to the oncogenic signaling axis of IGF1R/AKT.
LABORATORY INVESTIGATION
(2022)
Article
Chemistry, Medicinal
Fei Zhao, Yiran Wu, Fang Zhou, Dongxiang Xue, Simeng Zhao, Wanglong Lu, Xiaoyan Liu, Tao Hu, Yanli Qiu, Rongyan Li, Tangjie Gu, Yueming Xu, Fei Xu, Guisheng Zhong, Zhongxing Jiang, Suwen Zhao, Houchao Tao
Summary: This study investigates the activation mechanism of the smoothened receptor (SMO) and finds that active SMO has a rigid near assembly, while inactive SMO has a free far assembly and may be captured by cholesterol.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Yan Guo, Di Wu, QingJian Xu, Weihui Chen
Summary: The mandible is an important part of the craniofacial skeleton and its development involves multiple signaling pathways. The function of the hedgehog signaling pathway is crucial for mandibular development.
Article
Cell Biology
Yuqing Wang, Shanshan Lu, Yifei Chen, Liang Li, Xia Li, Zhongwei Qu, Junbo Huang, Liu Fan, Chao Yuan, Nan Song, Jun Zhang, Wendong Xu, Shenglian Yang, Yizheng Wang
Summary: The study demonstrated that the SHH-SMO-GLT-1 pathway can control extracellular glutamate and reduce ischemic brain damage by inhibiting SMO. It was found that under ischemic conditions, regulating the SHH-SMO-GLT-1 pathway can decrease the release of extracellular glutamate, thereby protecting neurons.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Review
Oncology
Minghao Li, Jiaxun Zhang, Haonan Zhou, Rong Xiang
Summary: Primary cilia, as microtubule-based structures, are closely related to the development of the central nervous system and play a crucial role in regulating the tumorigenesis of the central nervous system. The development of primary cilia can be regulated by several pathways, and primary cilia are also able to regulate a few signaling transduction pathways.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Gabriela Basile Carballo, Jessica Honorato Ribeiro, Giselle Pinto de Faria Lopes, Valeria Pereira Ferrer, Romulo Sperduto Dezonne, Claudia Maria Pereira, Tania Cristina Leite de Sampaio e Spohr
Summary: Glioblastoma is a common adult primary tumor of the CNS characterized by rapid growth and invasiveness. Resistance to chemotherapy in GBM may be due to cancer stem cells activating molecular pathways. Inhibiting the SHH signaling pathway induces apoptosis and autophagy in GBM cells, suggesting it as a potential therapeutic approach for refractory patients.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)