Article
Oncology
Daosen Chen, Xiaodiao Kang, Zhenxing Li, Liang Chen, Qiong Ma, Pei Fan
Summary: The study investigated the role of Hedgehog/GLI1 signaling pathway in regulating cisplatin resistance in osteosarcoma. Results showed that GLI1 was up-regulated in OS patients and cisplatin-resistant cells. Silencing GLI1 restored sensitivity to cisplatin and inhibited proliferation, migration, and colony formation, while increasing apoptosis. Furthermore, using a Hedgehog pathway inhibitor GANT61 in xenograft model demonstrated inhibition of tumor growth.
Article
Plant Sciences
Mengjie Li, Tingting Guo, Jiayi Lin, Xia Huang, Qiaodan Ke, Yujian Wu, Chunping Fang, Chenxia Hu
Summary: Curcumin, the main pharmacological component extracted from Curcuma longa L, has been found to inhibit proliferation and metastasis of TNBC cells via the Hedgehog/Gli1 pathway, providing potential therapeutic strategies for TNBC.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Minyu Wang, Wanying Huang
Summary: This study found that FOXS1 activates the Hedgehog (Hh) signaling pathway by blocking the ubiquitination of Gli1, thereby promoting the growth and metastasis of prostate cancer cells. High levels of FOXS1 were associated with worse tumor stage and shorter survival in prostate cancer patients.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Cell Biology
Weiyi Gong, Wenxuan Zhao, Gang Liu, Lei Shi, Xia Zhao
Summary: BDDD-721, a curcumin analogue, exhibits stronger anti-tumor activity than curcumin on medulloblastoma. It effectively inhibits the proliferation, migration, invasion, and promotes apoptosis of medulloblastoma cells. The study also discovered that BDDD-721 targets the Shh/Gli1 signaling pathway to exert its anticancer effects.
Article
Medicine, Research & Experimental
ZhongWei Wang, YaLi Wang, XiuLong Ma, ChengXue Dang
Summary: The study revealed that elevated expression of RSPO2 in nasopharyngeal carcinoma promotes cell survival and proliferation, while its silencing inhibits migration and invasion through regulation of EMT-related proteins and the ZNRF3/Hedgehog-Gli1 signaling pathway.
Article
Oncology
Zhuna Wu, Chunxian Huang, Ruixin Li, Hui Li, Huaiwu Lu, Zhongqiu Lin
Summary: Impaired radiosensitivity is a major cause of therapeutic failures in cervical cancer patients undergoing radical radiotherapy. The PRKCI gene, which exhibits tumor-specific copy number amplification in cervical cancer, is found to decrease radiosensitivity by modulating the Hh/GLI1 pathway.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiangyang Li, Rui Sun, Hao Wu, Chaonan Zheng, Ya-Qiu Long
Summary: English Summary: The Hedgehog/Glioma-associated oncogene (Hh/Gli) signaling pathway is crucial for embryonic development and tissue homeostasis, and its dysregulation is associated with various human malignancies. Gli1, a downstream transcription factor of the Hh pathway, is a common regulator of tumorigenic pathways in Hh-independent cancers, making it a promising drug target. However, the development of small molecules that target Gli1 protein has been slow due to lack of efficacy and selectivity. In this study, researchers developed novel Gli1 degraders based on the hydrophobic tagging (HyT) strategy, which effectively inhibited the proliferation of colorectal cancer cells and induced Gli1 degradation. These small molecules showed stronger potency in suppressing Hh target genes compared to the canonical Hh antagonist Vismodegib, and they overcame resistance to current Smoothened (SMO) antagonists. This study provides a new avenue for developing therapeutic approaches targeting the Hh/Gli1 signaling pathway.
BIOORGANIC CHEMISTRY
(2023)
Article
Oncology
Anke Koeniger, Anna Brichkina, Iris Nee, Lukas Dempwolff, Anna Hupfer, Ilya Galperin, Florian Finkernagel, Andrea Nist, Thorsten Stiewe, Till Adhikary, Wibke Diederich, Matthias Lauth
Summary: Elevated GLI1 expression levels are associated with improved survival in NB patients and GLI1 overexpression exerts tumor-suppressive traits in cultured NB cells. However, NB cells are protected from increased GLI1 levels as they have lost their primary cilia and ability to transduce Hedgehog signals. An isoxazole molecule (ISX) has been identified to activate GLI1 independently of primary cilia, providing a potential therapeutic strategy for NB treatment.
Article
Oncology
Jingkai Sun, Wenfeng Lin, Chaoming Li, Hideo Ueki, Ruizhi Xue, Takuya Sadahira, Hao Hu, Koichiro Wada, Na Li, Chunxiao Liu, Motoo Araki, Abai Xu, Peng Huang
Summary: Posaconazole inhibits tumor progression in embryonal rhabdomyosarcoma by inducing G0/G1 arrest and autophagy through downregulating Hedgehog signaling pathway, showing promising potential as an anti-tumor agent targeting ERMS.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Wei Wang, Taiqiang Yan, Wei Guo, Jianfang Niu, Zhiqing Zhao, Kunkun Sun, Hongliang Zhang, Yiyang Yu, Tingting Ren
Summary: The study identified a novel mechanism regulating HH-independent GLI1 expression in chondrosarcoma, involving the MVP protein and the mTOR/S6K1 signaling cascade. Inhibition of MVP and GLI1 together strongly suppressed tumor growth in vitro and in vivo. This finding provides a rationale for combination therapy in advanced chondrosarcoma patients.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Raphael Luis Rocha Nogueira, Tais Bacelar Sacramento de Araujo, Ludmila Faro Valverde, Viviane Aline Oliveira Silva, Bruno Raphael Ribeiro Cavalcante, Erik Aranha Rossi, Kyan James Allahdadi, Mitermayer Galvao dos Reis, Thiago Almeida Pereira, Ricardo D. Coletta, Daniel Pereira Bezerra, Bruno Solano de Freitas Souza, Rosane Borges Dias, Clarissa A. Gurgel Rocha
Summary: The present study evaluated the therapeutic potential of Arsenic Trioxide (ATO) in treating Oral Squamous Cell Carcinoma (OSCC). The results showed that ATO has antitumoral effects and inhibits the Hedgehog (HH) pathway. Furthermore, ATO also induced changes in cell morphology and cell cycle in oral cancer cells.
Article
Biochemistry & Molecular Biology
Randa Belgacemi, Soula Danopoulos, Gail Deutsch, Ian Glass, Valerian Dormoy, Saverio Bellusci, Denise Al Alam
Summary: The Hedgehog signaling pathway is essential for mouse lung development, and this study found similar expression patterns in human lung development. Inhibiting the Hedgehog signaling pathway in human lung development resulted in reduced branching and dysregulated epithelial-mesenchymal markers and related signaling pathways. These findings are important for exploring therapeutic targets for childhood pulmonary diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Shi-Hao Ni, Xiao-Jiao Zhang, Xiao-Lu OuYang, Tao-Chun Ye, Jin Li, Yue Li, Shu-Ning Sun, Xiao-Wei Han, Wen-Jie Long, Ling-Jun Wang, Zhong-Qi Yang, Lu Lu
Summary: This study demonstrates that long-term kidney damage and dialysis may lead to muscle wasting and ferroptosis, and Lobetyolin (LBT) may alleviate muscle injury by inhibiting ferroptosis through activation of the Hedgehog signaling pathway.
Article
Gastroenterology & Hepatology
Lu Zhuang, Yao Yao, Lisi Peng, Fang Cui, Cui Chen, Yang Zhang, Liqi Sun, Qihong Yu, Kun Lin
Summary: This study reveals that GSH2 is overexpressed in pancreatic cancer and silencing it can inhibit cell proliferation, migration, invasion, and increase sensitivity to gemcitabine. Silencing GSH2 alleviates gemcitabine resistance by activating the SHH/GLI1 pathway in pancreatic cancer, suggesting that targeting GSH2 could be a novel therapeutic strategy for PDAC.
DIGESTIVE DISEASES AND SCIENCES
(2022)
Review
Oncology
Justin T. Avery, Ruowen Zhang, Rebecca J. Boohaker
Summary: GLI1, a transcriptional effector in the Hedgehog signaling pathway, is tightly regulated during normal tissue development but aberrant activation in cancer can promote hallmarks such as proliferation, metastasis, and chemoresistance. Its oncogenic activities mainly involve regulating cell cycle, DNA replication, and DNA damage repair processes. Understanding the mechanisms of GLI1 dysregulation can provide prognostic and diagnostic biomarkers for targeted therapy in cancer treatment.
FRONTIERS IN ONCOLOGY
(2021)