Article
Cell Biology
Ping Shi, Jia Tian, Julianne C. Mallinger, Dahao Ling, Loic P. Deleyrolle, Jeremy C. Mcintyre, Tamara Caspary, Joshua J. Breunig, Matthew R. Sarkisian
Summary: This study found that increasing ARL13B expression in glioma cells can promote the accumulation of SMO and GLI2 in cilia, and this accumulation is resistant to SMO inhibitors. Furthermore, the increase in ARL13B also leads to changes in ciliary membrane characteristics and retrograde transport, which further promote SMO and GLI accumulation in glioma cells.
Review
Cell Biology
Chamey Suchors, James Kim
Summary: The Hedgehog signaling pathway is crucial for development and tissue regeneration, and its dysregulation has been linked to cancer. Our understanding of this pathway in tumorigenesis has significantly advanced over the past few decades. The pathway can have both tumor-suppressive and oncogenic functions, and noncanonical activation of GLI transcription factors has been observed in certain types of tumors.
Article
Oncology
Wenjing Huang, Han Liu, Wenfu Tan, Juan Wang
Summary: ABT-737 is identified as a selective Hh inhibitor that suppresses Hh signals far downstream of Smo and inhibits both wild-type and drug-resistant mutant Smo. It also delays the growth of drug-refractory Hh-dependent MB xenografts.
Article
Biochemistry & Molecular Biology
Junwan Fan, Haowen Li, Lun Kuang, Zichen Zhao, Wenyan He, Chen Liu, Yongjun Wang, Steven Y. Cheng, Wei Chen
Summary: A new Smoothened inhibitor, 0025A, has been discovered in this study, which effectively targets the Hedgehog signaling pathway and inhibits cancer cell activity. Additionally, it can suppress hair growth in mice.
CELL AND BIOSCIENCE
(2021)
Article
Cell Biology
Bo Lv, Xiao-Ou Zhang, Gregory J. Pazour
Summary: During Hedgehog signaling, Arih2 beta regulates the ER-associated degradation (ERAD) of Smo, preventing excess and potentially misfolded Smo from reaching the cilium and interfering with pathway regulation.
JOURNAL OF CELL SCIENCE
(2022)
Article
Chemistry, Medicinal
Li Chen, Maolun Liu, Han Yang, Shan Ren, Qiang Sun, Hui Zhao, Tianqi Ming, Shun Tang, Qiu Tao, Sha Zeng, Xianli Meng, Haibo Xu
Summary: It has been discovered that ursolic acid (UA), a compound found in medicinal herbs, has potent effects against colorectal cancer (CRC) by inhibiting non-canonical Hedgehog signaling. This study investigated the influence of UA on non-canonical Hedgehog signaling in CRC, and found that UA inhibited cell proliferation, induced apoptosis, and down-regulated signaling proteins in CRC cells. Furthermore, UA also improved symptoms, inhibited tumor growth, and induced apoptosis in a CRC xenograft model.
PHYTOTHERAPY RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Jian Yi Chai, Vaisnevee Sugumar, Mohammed Abdullah Alshawsh, Won Fen Wong, Aditya Arya, Pei Pei Chong, Chung Yeng Looi
Summary: The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved in mammals and plays crucial roles in cancer initiation and progression. GLI transcription factors are regulated by both SMO-dependent and SMO-independent mechanisms, with dysregulation leading to tumorigenesis in various cancers. Understanding the complex interplay between GLI and signaling elements could inspire new therapeutic breakthroughs for Hh-GLI-dependent cancers.
Review
Immunology
Yazhen Su, Hao Xing, Jie Kang, Linkun Bai, Liyun Zhang
Summary: The Hedgehog (Hh) signaling pathway plays a crucial role in rheumatic diseases and has the potential to be a therapeutic target.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Abbi Elise Smith, Elin Soley Sigurbjornsdottir, Eirikur Steingrimsson, Sara Sigurbjornsdottir
Summary: Hedgehog signalling plays a crucial role in development, anatomical arrangement, and tissue damage repair. Dysregulation of this pathway is associated with cancer, developmental disorders, and osteoarthritis. The pathway is conserved in most animals, and its activation is transduced through the receptor protein Smoothened and downstream effectors. Studies have shown that cholesterol binding is important for the activation of the pathway. In humans, a mutation in the Smoothened gene has been linked to a higher risk of hip osteoarthritis. Analysis of mouse models and human tissue suggests that hedgehog signalling is pathologically activated in chondrocytes of osteoarthritic cartilage.
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
Biochemistry & Molecular Biology
Chaohui Zhang, Yuxin Li, Jiaheng Cao, Beibei Yu, Kaiyue Zhang, Ke Li, Xinhui Xu, Zhikun Guo, Yinming Liang, Xiao Yang, Zhongzhou Yang, Yunfu Sun, Vesa Kaartinen, Keyue Ding, Jikui Wang
Summary: The study reveals that Smoothened-mediated hedgehog signaling controls posterior cardiac progenitor commitment, suggesting that Smoothened mutation may be involved in the etiology of congenital heart diseases related to the cardiac conduction system and heart valves.
Article
Cell Biology
Cintli C. Morales-Alcala, Ioanna Ch Georgiou, Alex J. Timmis, Natalia A. Riobo-Del Galdo
Summary: ITM2A negatively regulates both canonical and non-canonical Hh signaling pathways, serves as a negative regulator of PTCH1, and impacts autophagy and cell differentiation processes.
Article
Multidisciplinary Sciences
Rachel K. Lex, Weiqiang Zhou, Zhicheng Ji, Kristin N. Falkenstein, Kaleigh E. Schuler, Kathryn E. Windsor, Joseph D. Kim, Hongkai Ji, Steven A. Vokes
Summary: The study challenges the current understanding that GLI3 repression is established before Hedgehog (HH) signaling and demonstrates that GLI3 is inert in the limb bud before HH onset. The loss of Gli3 does not increase target gene expression or accessibility, contrasting with post-HH signaling. GLI repression is established independently of HH signaling, but after its onset.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ignazia Tusa, Sinforosa Gagliardi, Alessandro Tubita, Silvia Pandolfi, Alessio Menconi, Matteo Lulli, Persio Dello Sbarba, Barbara Stecca, Elisabetta Rovida
Summary: The study identified a novel Hedgehog-GLI-ERK5 axis that regulates melanoma cell growth, showing that activation of the Hedgehog-GLI pathway increased ERK5 expression and that inhibitors targeting both pathways were more effective in reducing melanoma cell viability and colony formation compared to single treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Tara Akhshi, William S. Trimble
Summary: The study reveals that Smo induces ciliogenesis through two distinct pathways while also activating autophagy, with the Gα(i)-LGN-NuMA-dynein complex playing a crucial role in the process. Different Smo agonists activate these pathways separately, and only together they can replicate the activity of Hh ligand.
JOURNAL OF CELL BIOLOGY
(2021)
Letter
Gastroenterology & Hepatology
Ken Liu, David Yeo, Michael Crawford, Simone I. Strasser, Geoffrey W. McCaughan
LIVER TRANSPLANTATION
(2021)
Letter
Pathology
Georgia McCaughan, Susan Jarvis, Joanne Joseph
Letter
Pathology
Nwe Ni Than, Simone Chin, James G. Kench, Geoff McCaughan, Avik Majumdar
Review
Cell & Tissue Engineering
Ary Marsee, Floris J. M. Roos, Monique M. A. Verstegen, Helmuth Gehart, Eelco de Koning, Frederic Lemaigre, Stuart J. Forbes, Weng Chuan Peng, Meritxell Huch, Takanori Takebe, Ludovic Vallier, Hans Clevers, Luc J. W. van der Laan, Bart Spee
Summary: HPB organoids are powerful tools for studying organ development, disease, and regeneration. By introducing a classification system and nomenclature, experts aim to standardize and validate these structures, while also addressing challenges to their clinical application.
Article
Biochemistry & Molecular Biology
Francis D. Gratte, Sara Pasic, N. Dianah B. Abu Bakar, Jully Gogoi-Tiwari, Xiao Liu, Rodrigo Carlessi, Tatiana Kisseleva, David A. Brenner, Grant A. Ramm, John K. Olynyk, Janina E. E. Tirnitz-Parker
Summary: Chronic liver injury involves continuous epithelial cell loss and inflammation, with hepatic wound healing processes including matrix deposition through activated HSCs and the expansion of LPCs. Recovery from previous TAA insult results in reduced disease progression and fibrosis, with coculture data showing that HSCs and LPCs communicate to regulate fibrogenesis, highlighting the role of LPCs as regulatory cells in chronic liver disease.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Benjamin J. Dwyer, Edward J. Jarman, Jully Gogoi-Tiwari, Sofia Ferreira-Gonzalez, Luke Boulter, Rachel V. Guest, Timothy J. Kendall, Dominic Kurian, Alastair M. Kilpatrick, Andrew J. Robson, Eoghan O'Duibhir, Tak Yung Man, Lara Campana, Philip J. Starkey Lewis, Stephen J. Wigmore, John K. Olynyk, Grant A. Ramm, Janina E. E. Tirnitz-Parker, Stuart J. Forbes
Summary: This study highlights the overexpression of TWEAK/Fn14 in human CCA and the upregulation of Fn14 during TAA-induced carcinogenesis. TWEAK modulates the secretion of factors from CCA cells, influencing the polarization of macrophages and promoting cancer-associated fibroblast proliferation in the tumor microenvironment.
JOURNAL OF HEPATOLOGY
(2021)
Review
Immunology
Ngee-Soon Lau, Andrew Jacques, Geoffrey McCaughan, Michael Crawford, Ken Liu, Carlo Pulitano
Summary: This review assesses technical advancements in split liver transplantation, such as in-situ splitting, machine perfusion, and arterial reconstruction. The use of in-situ splitting reduces cold ischemia time, while machine perfusion shows potential for improving graft quality. Additionally, the use of interposition grafts during split liver transplantation must be carefully considered due to increased risk of hepatic artery thrombosis.
TRANSPLANTATION REVIEWS
(2021)
Article
Medicine, General & Internal
Emily Nash, Abdul-Hamid Sabih, John Chetwood, Georgette Wood, Keval Pandya, Terry Yip, Avik Majumdar, Geoffrey W. McCaughan, Simone Strasser, Ken Liu
Summary: The study compared characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements, in a single center over a period of 2009-2020. It found that patients with paracetamol-related DILI had higher 90-day transplant-free survival rates compared to those with non-paracetamol DILI, especially cases involving herbal and dietary supplements. The proportion of DILI cases linked to herbal and dietary supplements has been increasing since 2009.
MEDICAL JOURNAL OF AUSTRALIA
(2021)
Article
Gastroenterology & Hepatology
Jess Howell, Avik Majumdar, Michael A. Fink, Mandy Byrne, Geoff McCaughan, Simone Strasser, Michael Crawford, Peter Hodgkinson, Katherine A. Stuart, Caroline Tallis, John Chen, Alan Wigg, Robert Jones, Bryon Jaques, Gary Jeffrey, Leon Adams, Michael C. Wallace, Stephen Munn, Ed Gane, Alex J. Thompson, Paul Gow
Summary: Since the introduction of universal access to DAAs in 2016 in Australia and New Zealand, the number and proportion of liver transplantations performed for HCV-related liver cirrhosis and HCC have decreased. This was also associated with a 31% reduction in death after liver transplantation.
LIVER TRANSPLANTATION
(2022)
Article
Oncology
Yen Ling Yeow, Jiansha Wu, Xiao Wang, Louise Winteringham, Kirk W. Feindel, Janina E. E. Tirnitz-Parker, Peter J. Leedman, Ruth Ganss, Juliana Hamzah
Summary: Improving tumor access for drug delivery, especially in poorly perfused tumors, is challenging. Specific ECM depletion using TNF alpha-CSG improves nanoparticle delivery into poorly perfused tumors such as HCC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Gastroenterology & Hepatology
Nofar Rosenberg, Matthias Van Haele, Tali Lanton, Neta Brashi, Zohar Bromberg, Hanan Adler, Hilla Giladi, Amnon Peled, Daniel S. Goldenberg, Jonathan H. Axelrod, Alina Simerzin, Chofit Chai, Mor Paldor, Auerlia Markezana, Dayana Yaish, Zohar Shemulian, Dvora Gross, Shanny Barnoy, Maytal Gefen, Osher Amran, Sofie Claerhout, Mirian Fernandez-Vaquero, Maria Garcia-Beccaria, Danijela Heide, Michal Shoshkes-Carmel, Dirk Schmidt Arras, Sharona Elgavish, Yuval Nevo, Hadar Benyamini, Janina E. E. Tirnitz-Parker, Aranzazu Sanchez, Blanca Herrera, Rifaat Safadi, Klaus H. Kaestner, Stefan Rose-John, Tania Roskams, Mathias Heikenwalder, Eithan Galun
Summary: This study reveals that combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) originates from hepatic progenitor cells (HPCs), not hepatocellular carcinoma (HCC). IL-6 plays a significant role in the aging process of HPCs, suggesting potential therapeutic targets for cHCC-CCA tumors.
JOURNAL OF HEPATOLOGY
(2022)
Article
Biochemical Research Methods
Alireza Mowla, Rose Belford, Julia Kohn-Gaone, Nathan Main, Janina E. E. Tirnitz-Parker, George C. Yeoh, Brendan F. Kennedy
Summary: Hepatocellular carcinoma, arising from cirrhosis, is a lethal cancer worldwide. The increased elasticity of the microenvironment due to chronic liver injury is a potential hepatocarcinogen, but its role is still not fully understood. This study proposes quantitative micro-elastography (QME) as a technique to map the micro-scale elasticity of liver tissue and correlate it with cellular scale cancerous mechanisms. Results of QME on mouse livers indicate a significant increase in elasticity caused by chronic liver injury, which correlates with pathological features such as fibrosis, hepatocyte damage, and immune cell infiltration, as shown in micro-elastograms.
BIOMEDICAL OPTICS EXPRESS
(2022)
Article
Medicine, Research & Experimental
Marti Cabanes-Creus, Renina Gale Navarro, Sophia H. Y. Liao, Suzanne Scott, Rodrig Carlessi, Ramon Roca-Pinilla, Maddison Knight, Grober Baltazar, Erhua Zhu, Matthew Jones, Elena Denisenko, Alistair R. R. Forrest, Ian E. Alexander, Janina E. E. Tirnitz-Parker, Lesze Lisowski
Summary: Recent clinical successes have increased interest in using adeno-associated virus (AAV) vectors for gene therapy. In this study, a liver xenograft mouse model was used to investigate the transcriptomic profile of human hepatocytes before and after engraftment. Furthermore, a set of rationally designed HSPG de-targeted AAV-LK03 variants were tested for their transduction performance in human hepatocytes, and the results demonstrated significantly improved lobular transduction profile in this model.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Cell Biology
Rodrigo Carlessi, Elena Denisenko, Ebru Boslem, Julia Kohn-Gaone, Nathan Main, N. Dianah B. Abu Bakar, Gayatri D. Shirolkar, Matthew Jones, Aaron B. Beasley, Daniel Poppe, Benjamin J. Dwyer, Connie Jackaman, M. Christian Tijam, Ryan Lister, Michael Karin, Jonathan A. Fallowfield, Timothy J. Kendall, Stuart J. Forbes, Elin S. Gray, John K. Olynyk, George Yeoh, Alistair R. R. Forrest, Grant A. Ramm, Mark A. Febbraio, Janina E. E. Tirnitz-Parker
Summary: By using single-nucleus RNA sequencing, researchers identified a disease-associated hepatocyte transcriptional state that is increasingly prevalent in chronic liver disease and associated with structural variants. Integrated analysis of human data confirmed this finding and revealed a correlation between high levels of this hepatocyte transcriptional state and an increased risk of hepatocellular carcinoma development.
Article
Oncology
Rodrigo Gularte-Merida, Shaleigh Smith, Anita S. Bowman, Arnaud da Cruz Paula, Walid Chatila, Craig M. Bielski, Monika Vyas, Laetitia Borsu, Ahmet Zehir, Luciano G. Martelotto, Jinru Shia, Rona Yaeger, Fang Fang, Rui Gardner, Ruibang Luo, Michael C. Schatz, Ronglai Shen, Britta Weigelt, Francisco Sanchez-Vega, Jorge S. Reis-Filho, Jaclyn F. Hechtman
Summary: Dual-driver mutations are found in a rare subset of colorectal cancer, often existing within the same tumor cells and across multiple tumor sites. Their presence and lower rate of allelic imbalance may be related to dose-dependent signaling within the mitogen-activated protein kinase pathway.
JCO PRECISION ONCOLOGY
(2022)