Article
Oncology
Julieta Afonso, Celine Goncalves, Marta Costa, Debora Ferreira, Lucio Santos, Adhemar Longatto-Filho, Fatima Baltazar
Summary: Glycolysis-related proteins are associated with bladder cancer aggressiveness and poor prognosis. The HK2 inhibitor 2-deoxy-D-glucose can inhibit glycolysis, reduce bladder cancer cell invasion, and increase sensitivity to cisplatin.
Review
Oncology
Katharina Joechle, Jessica Guenzle, Claus Hellerbrand, Pavel Strnad, Thorsten Cramer, Ulf Peter Neumann, Sven Arke Lang
Summary: mTORC2, a key effector of the PI3K/AKT/mTOR pathway, is associated with tumor growth, metastasis, and resistance to therapy. The central subunit Rictor of mTORC2 is upregulated in various cancers, linked to advanced tumor stages and poor prognosis, highlighting its significance in cancer development and treatment.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2021)
Review
Physiology
Varda Shoshan-Barmatz, Uttpal Anand, Edna Nahon-Crystal, Marta Di Carlo, Anna Shteinfer-Kuzmine
Summary: Metformin has been used to treat diabetes and other diseases since the late 1950s. Despite its opposite effects on different diseases, its involvement with VDAC1 suggests that it may be a key factor in metformin's impact on various diseases.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Neurosciences
Henry Querfurth, Han-Kyu Lee
Summary: mTOR is involved in regulating energy metabolism, neuronal growth, insulin signaling, and autophagy, playing both beneficial and pathogenic roles in neurodegenerative diseases. Balanced actions of mTOR complexes may have implications for Alzheimer's disease, Parkinson's disease, Huntington's disease, Frontotemporal dementia, and Amyotrophic Lateral Sclerosis. Beyond rapamycin, rapalogs with improved tolerability and delivery modes hold promise in treating age-related conditions.
MOLECULAR NEURODEGENERATION
(2021)
Article
Medicine, Research & Experimental
Mohamed El-Tanani, Hamdi Nsairat, Alaa A. Aljabali, Angel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Gowhar A. Naikoo, Walhan Alshaer, Murtaza M. Tambuwala
Summary: The mammalian target of rapamycin (mTOR), a signalling system, is necessary for various cell proliferation activities. It recognizes PI3KAKT stress signals as a serine-threonine kinase. The abnormal regulation of mTOR pathway has been proven to be crucial in cancer growth and advancement. This review primarily discusses the normal functions of mTOR as well as its abnormal roles in cancer development.
Article
Endocrinology & Metabolism
Calum Forteath, Ify Mordi, Raid Nisr, Erika J. Gutierrez-Lara, Noor Alqurashi, Iain R. Phair, Amy R. Cameron, Craig Beall, Ibrahim Bahr, Mohapradeep Mohan, Aaron K. F. Wong, Adel Dihoum, Anwar Mohammad, Colin N. A. Palmer, Douglas Lamont, Kei Sakamoto, Benoit Viollet, Marc Foretz, Chim C. Lang, Graham Rena
Summary: Using cellular approaches and proteomics, we found that metformin therapy for diabetes alters the regulation of branched chain amino acids through the suppression of the amino acid transporter SNAT2.
MOLECULAR METABOLISM
(2023)
Article
Pathology
Divya Sahu, Jianya Huan, Huawei Wang, Debashis Sahoo, Darren E. Casteel, Richard L. Klemke, Gerry R. Boss, Donna E. Hansel
Summary: Bladder cancer invasion is linked to mTORC2 activity, with increased iNOS expression identified as a key factor in invasion.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Review
Medicine, General & Internal
Zhenshan Ding, Wenwei Ying, Yuhui He, Xing Chen, Yangtian Jiao, Jianfeng Wang, Xiaofeng Zhou
Summary: The study systematically evaluated the diagnostic value of long-chain non-coding RNA urothelial carcinoembryonic antigen 1 (lncRNA-UCA1) for bladder cancer, finding that it has high clinical auxiliary diagnostic value and potential for further clinical application.
Article
Oncology
Jianya Huan, Petros Grivas, Jasmine Birch, Donna E. Hansel
Summary: The mammalian target of rapamycin (mTOR) pathway plays a crucial role in cell growth and metabolism. Dysregulation of this pathway can promote cancer growth and progression. Approximately 70% of bladder cancer (UC) cases show abnormal mTOR activity, indicating its key role in this cancer. This review highlights the importance of mTOR signaling in UC and its potential implications for future therapy. Despite extensive research on molecular alterations of the mTOR pathway in bladder cancer, there has been limited success in mTOR-targeted therapy. Further understanding of the signaling convergence onto mTOR complexes in bladder cancer may provide valuable insights for the treatment of this aggressive disease.
Article
Multidisciplinary Sciences
Xun Shangguan, Jianli He, Zehua Ma, Weiwei Zhang, Yiyi Ji, Kai Shen, Zhiying Yue, Wenyu Li, Zhixiang Xin, Quan Zheng, Ying Cao, Jiahua Pan, Baijun Dong, Jinke Cheng, Qi Wang, Wei Xue
Summary: The study reveals the crucial role of SUMOylation in regulating the binding of hexokinase 2 to mitochondria, impacting metabolic reprogramming and chemotherapy response in prostate cancer cells.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Alaa Abou Daher, Sahar Alkhansa, William S. Azar, Rim Rafeh, Hilda E. Ghadieh, Assaad A. Eid
Summary: Understanding the mechanisms behind diabetic nephropathy (DN) is crucial for developing effective treatments. The mTOR pathway has been identified as a key player in diabetes-induced kidney injury, through its involvement in insulin resistance, oxidative stress, and autophagy regulation.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Seishu Gen, Yu Matsumoto, Tsukasa Suzuki, Jun Inoue, Yuji Yamamoto
Summary: The tumor-suppressor protein TSC2 is regulated by insulin, energy, oxygen, and growth factors, and its dysfunction can lead to cell growth through activation of mTORC1. Methionine affects TSC2 stability and localization, and interacts with insulin signaling through TSC2 to modulate cell growth pathways.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Ophthalmology
Nozomi Igarashi, Megumi Honjo, Makoto Aihara
Summary: Glaucoma, the second leading cause of blindness worldwide, is often treated with trabeculectomy, but this surgery can lead to excessive scarring and tissue fibrosis. Studies have shown that mTOR inhibitors may offer a new treatment modality for reducing fibrotic response in human conjunctival fibroblasts and improving bleb scarring after filtration surgery.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Oncology
Daniela Simcikova, Dominik Gardas, Katerina Hlozkova, Martin Hruda, Petr Zacek, Lukas Rob, Petr Heneberg
Summary: The study revealed that depletion of HK1, but not HK2, in ovarian cancer cells increased sensitivity to high-dose metformin during glucose starvation. Additionally, HK1 was found to play a glycolysis-independent role in metabolism, even in glucose-free conditions, suggesting its involvement in a previously unknown HK1-metformin axis.
CANCER & METABOLISM
(2021)
Article
Rheumatology
Ecem Sevim, Salma Siddique, Madhavi Latha S. Chalasani, Susan Chyou, William D. Shipman, Orla O'Shea, Joanna Harp, Oral Alpan, Stephane Zuily, Theresa T. Lu, Doruk Erkan
Summary: This study investigated the activation of the mammalian target of rapamycin (mTOR) in the skin of patients with livedo and antiphospholipid antibodies (aPL). The results showed increased mTOR activity in the skin of aPL-positive patients, which may have implications for further research on the mTOR pathway in these patients.
JOURNAL OF RHEUMATOLOGY
(2022)