Article
Biochemistry & Molecular Biology
Ahlem Jebali, Maxime Battistella, Celeste Lebbe, Nicolas Dumaz
Summary: The network involving PI3K, AKT, and mTOR is important in melanoma oncogenesis, with RICTOR overexpression associated with poor prognosis. RICTOR enhances melanoma-initiating cells with stemness properties and contributes to resistance to BRAF inhibitors. An interaction between RICTOR and STAT3 in resistant cells, as well as a connection between RAS and RICTOR in resistant melanoma, were identified, suggesting RICTOR as a valuable therapeutic target in melanoma.
Article
Dermatology
Sen Guo, Qiao Yue, Shiyu Wang, Huina Wang, Zhubiao Ye, Weigang Zhang, Qiong Shi, Tianwen Gao, Chunying Li, Guannan Zhu
Summary: Sestrin2 plays a role in BRAFi resistance in melanoma cells and helps the cells adapt to higher oxidative stress. Knockdown of Sestrin2 activates mTOR signaling, and the combination of mTOR blockade and Sestrin2 ablation enhances the inhibition of melanoma cell growth.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2023)
Article
Oncology
Cedric Tehranian, Laura Fankhauser, Patrick N. Harter, Colin D. H. Ratcliffe, Pia S. Zeiner, Julia M. Messmer, Dirk C. Hoffmann, Katharina Frey, Dana Westphal, Michael W. Ronellenfitsch, Erik Sahai, Wolfgang Wick, Matthia A. Karreman, Frank Winkler
Summary: This study reveals the key role of the PAM pathway in critical steps of early brain metastasis and demonstrates the potential of its pharmacological inhibition as a preventive strategy for clinically relevant BM.
Article
Cell Biology
Dorota Gil, Marta Zarzycka, Joanna Pabijan, Ma lgorzata Lekka, Joanna Duli Dulinska-Litewka
Summary: Melanoma is resistant to chemotherapy and lacks fully effective targeted therapies. The mutations in melanoma lead to the hyperactivation of the MAPK and PI3K/AKT/mTOR pathways, which are responsible for abnormal protein synthesis. In this study, we investigated the effects of a specific PI3K/mTOR inhibitor, dactolisib, and Mnk inhibitor -CGP57380, alone and in combination on human melanoma cell lines. Both drugs showed inhibition of cell proliferation and migration when used individually, but their combination had additional antitumor effects. Simultaneous inhibition of both pathways may help overcome drug resistance.
CELLULAR SIGNALLING
(2023)
Article
Biochemical Research Methods
Ruizheng Sun, Yaozhong Liu, Cheng Lei, Zhenwei Tang, Lixia Lu
Summary: This study proposed and validated a novel 7-RNA based signature to predict the prognosis of wild-type BRAF cutaneous melanoma (WT Bf-CM) patients. Functional analysis suggested that the predictive function of this signature might be related to the up-regulation of RNA splicing, transcription, and cellular proliferation in the high-risk group. Additionally, the study found that the prognosis of WT Bf-CM patients is highly related to the PI3K/Akt/mTOR pathway.
BIOLOGICAL PROCEDURES ONLINE
(2022)
Article
Cell Biology
Jennifer L. Cotton, Kyvan Dang, Lu Hu, Yang Sun, Alka Singh, Mihir S. Rajurkar, Qi Li, Xu Wu, Junhao Mao
Summary: PTEN and LKB1 deficiency in Gli1-expressing gut mesenchymal cells, but not intestinal epithelium, drives polyp formation resembling human polyposis. Additionally, the study reveals the differential roles of PTEN and LKB1 in regulating the mTOR signaling pathway.
Review
Cell Biology
Mohammed Bourouh, Paola A. Marignani
Summary: Liver kinase B1 (LKB1) is a crucial tumor suppressor kinase that plays a role in various malignancies. It inhibits the growth and division of cancer cells by regulating metabolic pathways. Loss of LKB1 leads to metabolic reprogramming and promotes malignant growth of cancer cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Yinci Zhang, Jiaojiao Liang, Niandie Cao, Jiafeng Gao, Yinghai Xie, Shuping Zhou, Xiaolong Tang
Summary: This study found that ASIC1 alpha regulates the migration, invasion, and proliferation of liver cancer cells through the MMP-2/9/PI3K/AKT/mTOR pathway. Inhibition or knockdown of ASIC1 alpha can inhibit the migration, invasion, and proliferation of HepG2 and SK-Hep1 cells, while overexpression of ASIC1 alpha has the opposite effect. These findings provide new insights for the research of liver cancer chemotherapy.
Article
Integrative & Complementary Medicine
Du Bing-Xin, Lin Pei, Lin Jun
Summary: EGCG and ECG induce apoptosis through the mitochondrial signaling pathway and downregulate autophagy by modulating the AMPK/mTOR and PI3K/AKT/mTOR signaling pathways.
CHINESE JOURNAL OF NATURAL MEDICINES
(2022)
Article
Oncology
Faisal Hassan Tobeigei, Reem M. Gahtani, Ahmad Shaikh, Amer Al Ali, Nader Kameli, Hossam Kamli, Prasanna Rajagopalan
Summary: Malignant melanoma is characterized by genetic and molecular alterations that activate PI3K and RAS/BRAF pathways. Through high-throughput virtual screening, a lead molecule selectively targeting PI3K and BRAFV600E kinases was identified. In vitro cellular analysis confirmed the antiproliferative effects of the compound on melanoma cells.
Article
Cell Biology
Meng-Di Wu, Yuan-Ying Zhang, Shu-Ying Yi, Bei-Bei Sun, Jing Lan, Han-Ming Jiang, Gang-Ping Hao
Summary: In this study, the effects of Acetylshikonin (ASK) on apoptosis and autophagy in acute myeloid leukemia (AML) cells were investigated. The results showed that ASK induced apoptosis through the mitochondrial pathway and promoted autophagy via the LKB1/AMPK signaling pathway. ASK also suppressed the PI3K/Akt/mTOR pathway. These findings suggest that ASK-induced apoptosis in HL-60 cells is dependent on the activation of autophagy.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Yun Cai, Yi Liu, Ye Sun, Yu Ren
Summary: This study explored the role of MEOX2 in breast carcinoma and found that low levels of MEOX2 were associated with reduced overall survival in patients. Forced expression of MEOX2 inhibited cell proliferation, induced cell cycle arrest, restrained metastatic potential, and enhanced chemosensitivity. Mechanistically, MEOX2 negatively modulated the PI3K/AKT/mTOR and ERK1/2 pathways. The findings suggest that MEOX2 could be a potential target for anticancer therapy in breast carcinoma.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Yuxin Geng, Yulei Geng, Xiaoli Liu, Qiannan Chai, Xuejing Li, Taoran Ren, Qingli Shang
Summary: The study identified PI3K/AKT/mTOR pathway-related genes and developed a novel prognostic-related risk model in UVM. Three distinct subtypes with varying immune characteristics were identified, and a consensus machine learning-derived signature was developed as a potential biomarker for prognostic prediction in UVM patients.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Xianbo Wu, Yihua Xu, Qi Liang, Xinwei Yang, Jianli Huang, Jie Wang, Hong Zhang, Jianyou Shi
Summary: Studies have shown that PI3K/mTOR inhibitors are effective in cancer treatment, as they can inhibit cell proliferation and promote apoptosis. These inhibitors exhibit high potency and low drug resistance, indicating they have great potential as anticancer drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Immunology
Soheila Fattahi, Zahra Khalifehzadeh-Esfahani, Mina Mohammad-Rezaei, Sahar Mafi, Morteza Jafarinia
Summary: COVID-19 is a severe respiratory infection caused by SARS-CoV-2 and is a major global challenge. Although several effective COVID-19 vaccines have been developed, our understanding of specific therapeutic drugs for COVID-19 treatment is still limited. The mTOR pathway plays an important role in viral replication, and mTOR pathway inhibitors may be a potential approach to anti-SARS-CoV-2 therapy.
IMMUNOLOGIC RESEARCH
(2022)