Article
Gastroenterology & Hepatology
Yamin Zhao, Benjamin Schoeps, Dianbo Yao, Zhiheng Zhang, Kathleen Schuck, Vivien Tissen, Carsten Jaeger, Anna Melissa Schlitter, Rob van der Kammen, Christina Ludwig, Jan G. D'Haese, Susanne Raulefs, Nadja Maeritz, Shanshan Shen, Xiaoping Zou, Achim Krueger, Jorg Kleeff, Christoph W. Michalski, Helmut Friess, Metello Innocenti, Bo Kong
Summary: mTORC1 and mTORC2 play a dual, nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting the function of the Arp2/3 complex. The Arp2/3 complex acts as a common effector of mTORC1 and mTORC2, connecting oncogenic signals with actin dynamics in PDAC initiation.
Article
Cell Biology
Xuehong Yin, Ran Xue, Jing Wu, Muchen Wu, Bangxiang Xie, Qinghua Meng
Summary: PINK1 plays a role in the regulation of acute-on-chronic liver failure (ACLF) by affecting apoptosis-related factors via the mTORC2/AKT signaling pathway. The findings of this study provide a theoretical basis for the clinical application of PINK1 as a valid target for ACLF treatment.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Aaron Seth Tooley, Dubek Kazyken, Cagri Bodur, Ian E. Gonzalez, Diane C. Fingar
Summary: TBK1 can directly activate mTOR complex 2 (mTORC2) to promote Akt phosphorylation, involving in cellular metabolism and proliferation. Interaction between TBK1 and mTOR serves as key nodes in two major signaling networks.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Fisheries
Zhimeng Lv, Zongxu Yue, Yina Shao, Chenghua Li, Xuelin Zhao, Ming Guo
Summary: Endocytosis plays a crucial role in the immune defense systems of invertebrates, with mTORC2 and the AGC kinase family interacting to regulate this process. The unique subunit protein Rictor is essential for mTORC2 function and plays a key role in endocytosis. Knockdown of AjRictor and inhibition of mTORC2 activity resulted in a significant decrease in endocytosis rate in sea cucumber coelomocytes, highlighting the important regulatory role of mTORC2/Rictor in immune defense against pathogen invasion.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Biology
Polina Kosillo, Kamran M. Ahmed, Erin E. Aisenberg, Vasiliki Karalis, Bradley M. Roberts, Stephanie J. Cragg, Helen S. Bateup
Summary: The mTOR pathway is crucial for regulating cell growth and metabolism, and it plays a particularly important role in midbrain dopamine neurons. This study investigated the effects of mTORC1 and mTORC2 complexes on dopamine neuron properties. The inhibition of mTORC1 had significant and broad impacts on dopamine neuron structure and function, while the inhibition of mTORC2 had more subtle effects. Disruption of both mTOR complexes resulted in pronounced deficits in dopamine release.
Article
Neurosciences
Kristin D. Dahl, Adam R. Almeida, Hannah A. Hathaway, Jennifer Bourne, Tanya L. Brown, Lisbet T. Finseth, Teresa L. Wood, Wendy B. Macklin
Summary: In the Central Nervous System (CNS), oligodendrocyte progenitor cells (OPCs) differentiate into mature oligodendrocytes that generate myelin, crucial for normal nervous system function. This study focused on the role of mTORC2 signaling in OPCs using PDGFRa-Cre X Rictorfl/fl mice. Loss of mTORC2 in OPCs led to early reduction in myelin RNAs and proteins, with more severe hypomyelination and increased unmyelinated axons observed in the corpus callosum compared to the spinal cord. The study revealed regionally specific effects of mTORC2 signaling in OPCs, particularly in the corpus callosum.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Immunology
Hongkai Zhuang, Shujie Wang, Bo Chen, Zedan Zhang, Zuyi Ma, Zhenchong Li, Chunsheng Liu, Zixuan Zhou, Yuanfeng Gong, Shanzhou Huang, Baohua Hou, Yajin Chen, Chuanzhao Zhang
Summary: The study established a specific HIF-1 score system to discriminate PDAC with various hypoxia statuses and immune microenvironments. For highly hypoxic and immunosuppressive tumors, a combination treatment strategy should be considered in the future.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yue Zhang, Xinman Du, Xuemei Chen, Hongyu Tang, Qin Zhou, Junlin He, Yubin Ding, Yingxiong Wang, Xueqing Liu, Yanqing Geng
Summary: This study demonstrates the important role of Rictor in regulating uterine receptivity, which is crucial for both mice and humans. Loss of Rictor leads to impaired fertility and altered expression in the endometrium of women with infertility.
Article
Chemistry, Multidisciplinary
Hui-Lu Zhang, Ping Chen, He-Xin Yan, Gong-Bo Fu, Fei-Fei Luo, Jun Zhang, Shi-Min Zhao, Bo Zhai, Jiang-Hong Yu, Lin Chen, Hao-Shu Cui, Jian Chen, Shuai Huang, Jun Zeng, Wei Xu, Hong-Yang Wang, Jie Liu
Summary: Liver cancer cells display stem-like characteristics upon glutamine shortage and promote transformation into stem-like cells. Increased expression of glutamine synthetase is essential for maintaining and promoting stem-like characteristics. Mechanistically, glutamine starvation activates Rictor/mTORC2 pathway to induce HDAC3-mediated deacetylation and stabilization of glutamine synthetase.
Article
Multidisciplinary Sciences
James Okoh, Jacqunae Mays, Alexandre Bacq, Juan A. Oses-Prieto, Stefka Tyanova, Chien-Ju Chen, Khalel Imanbeyev, Marion Doladilhe, Hongyi Zhou, Paymaan Jafar-Nejad, Alma Burlingame, Jeffrey Noebels, Stephanie Baulac, Mauro Costa-Mattioli
Summary: Inhibition of mTORC2 suppresses seizures in animal models with multiple etiologies, thereby enhancing neuronal resilience to the pathological hypersynchrony associated with epilepsy.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Xiaoxue Jiang, Kan Liu, Haizhou Jiang, Hanrui Yin, En-duo Wang, Hong Cheng, Feixiang Yuan, Fei Xiao, Fenfen Wang, Wei Lu, Bo Peng, Yousheng Shu, Xiaoying Li, Shanghai Chen, Feifan Guo
Summary: This study demonstrates that lysosomal amino acid accumulation is associated with insulin resistance, highlighting the role of lysosomal membrane protein SLC7A14 in promoting insulin resistance. SLC7A14 acts as a transporter leading to the accumulation of lysosomal γ-aminobutyric acid (GABA), which inhibits mTORC2 activity and induces insulin resistance. The findings suggest that targeting SLC7A14 may provide a therapeutic approach for treating insulin resistance and GABA-related diseases, as well as providing insights into the upstream mechanisms of mTORC2.
Article
Cell & Tissue Engineering
Shan-Shan Meng, Feng-Mei Guo, Li-Li Huang, Ying-Zi Huang, Jian-Feng Xie, Cong-Shan Yang, Hai-Bo Qiu, Yi Yang
Summary: HGF promotes the reconstruction of vascular endothelial barrier function through mTORC2 and mTORC1 pathways, indicating potential therapeutic effects on ALI/ARDS.
STEM CELLS INTERNATIONAL
(2021)
Article
Oncology
Rui-zhen Cao, Li Min, Si Liu, Ru-yue Tian, Hai-yan Jiang, Juan Liu, Lin-lin Shao, Rui Cheng, Sheng-tao Zhu, Shui-long Guo, Peng Li
Summary: The study revealed that Rictor is upregulated in gastric cancer and associated with worse prognosis. It inhibits tumor cell apoptosis and activates Cav 1 through the Akt signaling pathway. Therefore, Rictor may serve as a potential prognostic biomarker and therapeutic target in gastric cancer patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jia-dan Wang, Ying Shao, Dan Liu, Nuo-ya Liu, Dan-yan Zhu
Summary: In this study, we elucidated the mechanisms of mitochondrial damage in ESC-CMs after knockdown of Rictor using a model of cardiomyocyte differentiation from mouse ES cells. Knockdown of Rictor led to swollen and ruptured mitochondria, decreased ATP production and mitochondrial transmembrane potential, inhibited mitochondrial respiratory chain complex activities, and hindered Cx43 translocation into mitochondria, ultimately resulted in mitochondrial dysfunction in ESC-CMs.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Biochemistry & Molecular Biology
Jia-Mei Wang, Qi Gao, Qi Zhang, Liang Hao, Jing-Yi Jiang, Ling-Yue Huyan, Bao-Qin Liu, Jing Yan, Chao Li, Hua-Qin Wang
Summary: The study found decreased expression of BAG5 in cisplatin-resistant ovarian cancer cells and tissues. BAG5 knockdown was involved in metabolic reprogramming and maintenance of cancer stem cell-like features by regulating the Rictor-mTORC2 pathway. Upregulation of Bcl6 repressed BAG5 transcription in cisplatin-resistant ovarian cancer. The study identified the Bcl6/BAG5/Rictor-mTORC2 pathway in metabolic reprogramming and maintenance of cancer stem cell-like features in cisplatin-resistant ovarian cancer cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)