Review
Biochemistry & Molecular Biology
Jessika Poliana Teixeira, Teodorico Castro Ramalho
Summary: Autism Spectrum Disorder (ASD) is a disorder characterized by changes in social and cognitive skills, but the etiology is complex and therapeutic progress is limited. Dysfunctions in synaptic protein synthesis observed in patients with ASD may be targeted through research on the mTOR pathway for potential new treatments.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Patrick Senechal, Francis Robert, Regina Cencic, Akiko Yanagiya, Jennifer Chu, Nahum Sonenberg, Marilene Paquet, Jerry Pelletier
Summary: The translation initiation factor eIF4F is crucial for cap-dependent protein synthesis initiation. Different subunits of eIF4F have varying roles in development and tumorigenesis, with some being essential for viability and tumor onset, while others have non-essential functions. This study highlights the complex roles of different eIF4F subunits in gene expression regulation during embryogenesis and tumor development.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Oncology
Qiong Wu, Jiali Ma, Jue Wei, Wenying Meng, Yugang Wang, Min Shi
Summary: FOXD1-AS1 aggravates gastric cancer progression and chemoresistance by promoting FOXD1 translation through the PIK3CA/PI3K/AKT/mTOR signaling pathway. These findings offer a potential novel target for treating gastric cancer patients, especially those with cisplatin resistance.
MOLECULAR ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Suyin Ge, Qingqing Zhang, Yonglin Chen, Yizhen Tian, Ruiying Yang, Xu Chen, Fang Li, Baolai Zhang
Summary: Ribavirin shows anti-cancer efficacy in colorectal cancer by inhibiting cell proliferation and colony formation, potentially through reducing PRMT5 and eIF4E protein levels.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Tao Liu, Xiangsen Liang, Yu Sun, Shengzhuang Yang
Summary: The study revealed that SIRT1 expression was upregulated in EC, and rapamycin suppressed cell viability, migration, invasion, and the PI3K/AKT/mTOR signaling pathway in EC by negatively regulating SIRT1.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Review
Chemistry, Medicinal
Shuo Li, Jia-shu Chen, Xiangqian Li, Xiaoyi Bai, Dayong Shi
Summary: Overexpression of eIF4E is common in various solid tumors and hematologic cancers, making it a potential anti-cancer target. This review provides a detailed classification and description of the anti-cancer activities of promising compounds, concluding that MNK1/2 and eIF4E/eIF4G interaction inhibitors are superior to mTOR inhibitors for targeted therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Benjamin Weiss, Pascale Jaquier-Gubler, Joseph Alphonsus Curran
Summary: This study focuses on a series of cellular molecular processes during translation initiation, including recruitment of small ribosome, recognition of mRNA, and the impact of eIF4E-5' cap interaction in the context of different TL lengths. The findings reveal the significance of these molecular interactions in protein synthesis and provide insights into the current recruitment models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Sheikh Tahir Majeed, Asiya Batool, Rabiya Majeed, Nadiem Nazir Bhat, Muhammad Afzal Zargar, Khurshid Iqbal Andrabi
Summary: Phosphorylated S209-eIF4E interacts with the TOS motif of S6K1, releasing it from auto-inhibition and priming it for activation in an mTORC1-independent manner. The role of mTORC1 is limited to engaging eIF4E with the S6K1-TOS motif to influence S6K1's state of activation.
Review
Biochemistry & Molecular Biology
Antonino Glaviano, Aaron S. C. Foo, Hiu Y. Lam, Kenneth C. H. Yap, William Jacot, Robert H. Jones, Huiyan Eng, Madhumathy G. Nair, Pooyan Makvandi, Birgit Geoerger, Matthew H. Kulke, Richard D. Baird, Jyothi S. Prabhu, Daniela Carbone, Camilla Pecoraro, Daniel B. L. Teh, Gautam Sethi, Vincenzo Cavalieri, Kevin H. Lin, Nathalie R. Javidi-Sharifi, Eneda Toska, Matthew S. Davids, Jennifer R. Brown, Patrizia Diana, Justin Stebbing, David A. Fruman, Alan P. Kumar
Summary: The PI3K/AKT/mTOR (PAM) signaling pathway plays a crucial role in cell survival, growth, and cell cycle progression. Dysregulation of this pathway is associated with cancer development and resistance to therapy. This review focuses on the major dysregulations in the PAM signaling pathway in cancer and discusses strategies for overcoming treatment resistance. The role of PAM signaling in immunology and immunotherapies is also discussed.
Article
Oncology
Jida Guo, Shengqiang Zhang, Jun Wang, Pengfei Zhang, Tong Lu, Linyou Zhang
Summary: This study demonstrates the inhibitory effect of Hinokiflavone (HF) on the growth and progression of esophageal squamous cell carcinoma (ESCC). The underlying mechanism involves blocking the PI3K/AKT/mTOR signaling pathway, resulting in suppressed cell proliferation and induced apoptosis. HF could potentially serve as a complementary/alternative agent in the treatment of ESCC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Trang Uyen Nguyen, Harrison Hector, Eric Nels Pederson, Jianan Lin, Zhengqing Ouyang, Hans-Guido Wendel, Kamini Singh
Summary: Pancreatic cancer is a aggressive cancer with a low survival rate. In this study, we explored the effect of inhibiting protein synthesis and its role in inducing feedback mechanisms that may impact the therapeutic response. We found that rapamycin treatment inhibited the synthesis of proteins required for cancer cell growth, but also induced the synthesis of proteins that limited the anti-tumor effect of rapamycin. However, the combination of rapamycin with the small molecule inhibitor CR-1-31-B increased the efficacy of rapamycin.
Review
Pharmacology & Pharmacy
Nazanin Momeni Roudsari, Naser-Aldin Lashgari, Saeideh Momtaz, Shaghayegh Abaft, Fatemeh Jamali, Pardis Safaiepour, Kiyana Narimisa, Gloria Jackson, Anusha Bishayee, Nima Rezaei, Amir Hossein Abdolghaffari, Anupam Bishayee
Summary: The importance of the PI3K/Akt/mTOR pathway in prostate cancer treatment and the clinical applications of natural agents and small molecule inhibitors targeting this pathway are discussed in the study. Research suggests that natural mTOR inhibitors can interfere with the PI3K/Akt/mTOR pathway through multiple mechanisms, with inhibition of Akt and suppression of mTOR 1 activity being the main therapeutic approaches. Combination therapy has been shown to improve the efficacy of these inhibitors in suppressing prostate cancer progression or overcoming resistance by cancer cells.
Article
Pathology
Zhaoyang Yan, Tongxin Xu, Juntao Lu, Zheng Wu, Xiaoxu Li, Jinsheng Xu, Wei Guo, Zhiming Dong
Summary: NRSN2 is upregulated in esophageal squamous cell carcinoma (ESCC) and is associated with malignancy and poor prognosis. NRSN2 is transcribed by E2F1 and promotes proliferation, migration, and invasion of ESCC cells by activating the AKT/mTOR pathway.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Chemistry, Medicinal
Patrick D. Fischer, Evangelos Papadopoulos, Jon M. Dempersmier, Zi-Fu Wang, Radoslaw P. Nowak, Katherine A. Donovan, Joann Kalabathula, Christoph Gorgulla, Pierre P. M. Junghanns, Eihab Kabha, Nikolaos Dimitrakakis, Ognyan Petrov, Constantine Mitsiades, Christian Ducho, Vladimir Gelev, Eric S. Fischer, Gerhard Wagner, Haribabu Arthanari
Summary: The translation initiation factor eIF4E is a key regulator of cap-dependent protein synthesis, with overexpression implicated in diseases like cancer. A novel inhibitor, i4EG-BiP, has been shown to displace eIF4G and inhibit cancer cell proliferation. Efforts to design PROTACs targeting eIF4E for proteasomal degradation have faced challenges, such as competitive effects from 4E-BP1 binding.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Stacey L. Lehman, Evan D. Wilson, Kevin Camphausen, Philip J. Tofilon
Summary: Research suggests that targeting proteins involved in the translational machinery can increase the sensitivity of tumor cells to radiotherapy, thereby improving efficacy. Inhibiting key proteins in the translation initiation machinery can reduce protein expression and potentially impact DNA repair, making tumor cells more susceptible to the effects of radiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)