Article
Biochemistry & Molecular Biology
Irina Giralt, Gabriel Gallo-Oller, Natalia Navarro, Patricia Zarzosa, Guillem Pons, Ainara Magdaleno, Miguel F. Segura, Constantino Sabado, Raquel Hladun, Diego Arango, Jose Sanchez de Toledo, Lucas Moreno, Soledad Gallego, Josep Roma
Summary: The study demonstrates the therapeutic potential of DKK-1 pharmaceutical inhibition in rhabdomyosarcoma, resulting in beta-catenin activation and modulation of focal adhesion kinase, with positive effects on myogenic marker expression and a reduction in proliferation and invasion. In addition, the chemical inhibitor WAY-262611 was able to impair tumor cell survival in vivo, suggesting DKK-1 as a potential molecular target for novel therapeutic strategies in RMS patients, especially those with high DKK-1 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Michael Latour, Nam-Gu Her, Santosh Kesari, Elmar Nurmemmedov
Summary: The WNT signaling pathway plays a crucial role in glioblastoma genesis and therapy resistance, presenting a therapeutic challenge. Current targeted therapies under clinical investigation may offer new treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Khalid Saad Alharbi, Waleed Hassan Almalki, Hafiz A. Makeen, Mohammed Albratty, Abdulkarim M. Meraya, Rupak Nagraik, Avinash Sharma, Deepak Kumar, Dinesh Kumar Chellappan, Sachin Kumar Singh, Kamal Dua, Gaurav Gupta
Summary: Breast cancer is a challenging cancer to treat, but nutraceuticals can be a beneficial supplementary therapy in reducing disease severity, limiting malignant cell growth, and modifying cancer-related mechanisms.
JOURNAL OF FOOD BIOCHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Man Zhang, Jinhua Zheng, Junying Guo, Qiujin Zhang, Juan Du, Xiangfeng Zhao, Zhihua Wang, Qinyuan Liao
Summary: Breast cancer has the highest incidence rate in the world, and therapy resistance of breast cancer stem cells (CSCs) poses a major challenge in clinical treatment. This study identifies SIA-IgG as a potential therapeutic target in breast cancer and investigates its functional changes and molecular mechanisms. The results provide a potential prognostic marker and a novel therapeutic target for breast cancer.
Review
Chemistry, Medicinal
Panpan Yang, Yumeng Zhu, Qinwen Zheng, Sha Meng, Yongya Wu, Wen Shuai, Qiu Sun, Guan Wang
Summary: The Wnt/fl-catenin signaling pathway is involved in various cellular processes and its abnormal activation has been linked to cancer development. Fl-catenin, a core component of this pathway, is a key factor in its activation. Therefore, the development of Fl-catenin inhibitors has become an important focus in anticancer drug research. However, challenges in terms of selectivity, specificity, and physicochemical properties need to be addressed. This review highlights the progress made in the research of small molecule inhibitors targeting Fl-catenin and discusses the future prospects in drug development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biology
Sayumi Fujimori, Izumi Ohigashi, Hayato Abe, Yosuke Matsushita, Toyomasa Katagiri, Makoto M. Taketo, Yousuke Takahama, Shinji Takada
Summary: The thymic epithelium plays a crucial role in supporting the development of T cells. This study found that enhanced expression of beta-catenin in thymic epithelial cells leads to thymic dysplasia and T cell deficiency in the embryonic period, while loss of beta-catenin function only slightly reduces cortical thymic epithelial cells and thymocytes in postnatal development.
Article
Multidisciplinary Sciences
Morgane Le Rolle, Filippo Massa, Pam Siggers, Laurent Turchi, Agnes Loubat, Bon-Kyoung Koo, Hans Clevers, Andy Greenfield, Andreas Schedl, Marie-Christine Chaboissier, Anne-Amandine Chassot
Summary: This study shows that germ cell-intrinsic beta-catenin activity in mouse embryonic ovaries is essential for maintaining pluripotency and its repression is crucial for differentiation and meiosis entry. The interaction of beta-catenin with the pluripotent-associated factor POU5F1 in the nucleus is associated with germ cell pluripotency, and its exit from the nucleus correlates with germ cell differentiation. These findings highlight the role of beta-catenin as a central gatekeeper in ovarian differentiation and gametogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pathology
Jenesis Gayden, Shikai Hu, Paul N. Joseph, Evan Delgado, Silvia Liu, Aaron Bell, Stephanie Puig, Satdarshan P. Monga, Zachary Freyberg
Summary: Hepatic zonation is crucial for liver function, and Wnt signaling plays a key role in this process. However, the expression of Wnt signaling components, particularly all 10 Frizzled receptors, in adult liver has not been fully characterized. In this study, the spatial expression of Fzd receptors was mapped in adult mouse liver, revealing that Fzd receptors 1, 4, and 6 were the most highly expressed. While most Wnt signaling occurred in zone 3, the expression of Fzd receptors did not show zonation. However, Fzd receptor 6 was preferentially expressed in zone 1. The study also showed that Fzd receptors and Wnts were not uniformly expressed by all hepatic cell types. These findings provide a foundation for future functional studies of Fzd receptors in healthy and diseased liver states.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Oncology
Fatma Nihan Akkoc Mustafayev, Mihir Amitabh Shukla, Amanda Lanier, Denai R. Milton, Angelica M. Gutierrez, Stephen K. Gruschkus, John E. Lewis, Rashmi K. Murthy, Banu K. Arun
Summary: BRCA1/2 mutations occurred in 6.6% of patients with human epidermal growth factor receptor 2 (HER2/neu)-positive breast cancer. However, BRCA mutation status did not affect survival outcomes in patients who had HER2/neu-positive breast cancer.
Review
Biochemistry & Molecular Biology
Sarah Koushyar, Valerie S. Meniel, Toby J. Phesse, Helen B. Pearson
Summary: Aberrant activation of the Wnt pathway is closely related to tumor formation, progression, and therapeutic resistance in prostate cancer. Targeting the Wnt pathway for prostate cancer treatment has shown potential efficacy. However, the functional consequences of activating the Wnt pathway during different stages of prostate cancer progression are still unclear. Preclinical research on targeting Wnt signaling in the treatment of prostate cancer is crucial for identifying effective treatment strategies and improving patient care.
Article
Immunology
Safaa A. Faheem, Reem M. Hazem, Norhan M. Elsayed, Yasser M. Ahmed, Noha M. Saeed
Summary: The study aimed to assess the involvement of Wnt/beta-catenin signaling in CsA-induced hepatotoxicity and whether knockdown of this pathway by NCL can attenuate CsA-induced hepatotoxicity. The results showed that NCL can significantly decrease liver enzymes activities, improve histopathological alterations induced by CsA, alleviate oxidative stress and inflammation. Moreover, NCL inhibited Wnt/beta-catenin signaling and increased the expression of PPAR-gamma.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Oncology
Hazel M. Quinn, Regina Vogel, Oliver Popp, Philipp Mertins, Linxiang Lan, Clemens Messerschmidt, Alexandro Landshammer, Kamil Lisek, Sophie Chateau-Joubert, Elisabetta Marangoni, Elle Koren, Yaron Fuchs, Walter Birchmeier
Summary: The research reveals that in basal-like breast cancers, YAP signaling is essential for beta-catenin activity, controlling the cancer stem cell (CSC) program. Targeting the YAP/TEAD4/beta-catenin complex may offer a potential therapeutic strategy for eradicating CSCs in basal-like breast cancers.
Review
Biochemistry & Molecular Biology
Ahmed Omran, Diana Atanasova, Filip Landgren, Per Magnusson
Summary: This article reviews recent progress in the study of SOST gene, including the regulation pathways, structural and functional properties of sclerostin, and its pathophysiology. It also introduces the development of new assay methods and the importance of standardization work.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Mingfeng Yu, Yuchao Yang, Matthew Sykes, Shudong Wang
Summary: Tankyrases are multifunctional enzymes that regulate various biological processes, including telomere maintenance and cellular signaling. Their involvement in human diseases, especially cancer, has led to increased interest in tankyrase inhibitors as potential therapeutics. This review provides an overview of tankyrases and their cancer-related functions, and discusses the progress of small-molecule inhibitors targeting tankyrases, including their binding modes and clinically trialed inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Lisa Gruentkemeier, Aditi Khurana, Farideh Zamaniyan Bischoff, Oliver Hoffmann, Rainer Kimmig, Mathew Moore, Philip Cotter, Sabine Kasimir-Bauer
Summary: The study utilized the DEPArray(TM) system for HER2/FISH analysis, which can identify HER2/FISH discordance in BC patients, aiding in determining the need for anti-HER2 therapy.
Article
Oncology
Anthony B. Mak, Allison M. L. Nixon, Jason Moffat
Article
Biochemistry & Molecular Biology
Anthony B. Mak, Mariana Pehar, Allison M. L. Nixon, Rashida A. Williams, Andrea C. Uetrecht, Luigi Puglielli, Jason Moffat
JOURNAL OF MOLECULAR BIOLOGY
(2014)
Article
Cell Biology
Anthony B. Mak, Allison M. L. Nixon, Saranya Kittanakom, Jocelyn M. Stewart, Ginny I. Chen, Jasna Curak, Anne-Claude Gingras, Ralph Mazitschek, Benjamin G. Neel, Igor Stagljar, Jason Moffat
Article
Multidisciplinary Sciences
Allison M. L. Nixon, Alejandro Duque, Nicholas Yelle, Megan McLaughlin, Sadegh Davoudi, Nicolas M. Pedley, Jennifer Haynes, Kevin R. Brown, James Pan, Traver Hart, Penney M. Gilbert, Sheila K. Singh, Catherine A. O'Brien, Sachdev S. Sidhu, Jason Moffat
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Sumaiyah K. Rehman, Jennifer Haynes, Evelyne Collignon, Kevin R. Brown, Yadong Wang, Allison M. L. Nixon, Jeffrey P. Bruce, Jeffrey A. Wintersinger, Arvind Singh Mer, Edwyn B. L. Lo, Cherry Leung, Evelyne Lima-Fernandes, Nicholas M. Pedley, Fraser Soares, Sophie McGibbon, Housheng Hansen He, Aaron Pollet, Trevor J. Pugh, Benjamin Haibe-Kains, Quaid Morris, Miguel Ramalho-Santos, Sidhartha Goyal, Jason Moffat, Catherine A. O'Brien
Summary: It has been discovered that cancer cells enter a drug-tolerant persister state to evade treatment, showing similarities with diapause in embryonic development. All cancer cells possess the potential to become drug-tolerant persisters, rather than just a small subpopulation.
Article
Oncology
Chewei Anderson Chang, Jayu Jen, Shaowen Jiang, Azin Sayad, Arvind Singh Mer, Kevin R. Brown, Allison M. L. Nixon, Avantika Dhabaria, Kwan Ho Tang, David Venet, Christos Sotiriou, Jiehui Deng, Kwok-Kin Wong, Sylvia Adams, Peter Meyn, Adriana Heguy, Jane A. Skok, Aristotelis Tsirigos, Beatrix Ueberheide, Jason Moffat, Abhyudai Singh, Benjamin Haibe-Kains, Alireza Khodadadi-Jamayran, Benjamin G. Neel
Summary: Resistance to targeted therapies in HER2-positive breast cancer is often attributed to the presence of drug-tolerant persisters (DTPs). This study reveals that HER2 TKI treatment leads to the emergence of DTPs with different transcriptomes, and these DTPs are originated from pre-DTP cells that cycle stochastically. The findings provide insights into the ontogeny of DTPs and potential vulnerabilities for therapeutic targeting.