Article
Oncology
Rahim Ullah, Qing Yin, Aidan H. Snell, Lixin Wan
Summary: The RAF-MEK-ERK signaling cascade is a well-characterized MAPK pathway that plays a critical role in cell proliferation and survival. Genetic alterations in this pathway are highly prevalent in human cancers and can lead to uncontrolled cell growth and tumor formation. The crosstalk between the RAF-MEK-ERK axis and other signaling pathways further enhances its proliferative potential in human cancers.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Neurosciences
Jiao Ma, Zhechun Hu, Huimin Yue, Yujian Luo, Chao Wang, Xuan Wu, Yan Gu, Lang Wang
Summary: In this study, the researchers found that the metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs) and plays a crucial role in regulating their development and functional integration. Lack of GRM2 leads to developmental defects and impaired cognitive functions in the hippocampus. Interestingly, knocking down GRM2 resulted in the excessive activation of the MEK/ERK1/2 pathway, which was ameliorated by inhibiting MEK.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Plant Sciences
Guowei Gong, Yuzhong Zheng, Xiangpeng Kong, Zhen Wen
Summary: Ononin, a bioactive compound found in functional foods or plants, has been shown to exhibit anticancer properties in both in vitro and in vivo studies. In this study, ononin was also found to inhibit endothelial cell angiogenesis and suppress tumor cell proliferation. The potential role of ononin as a candidate for prevention and treatment of angiogenesis-related diseases was highlighted in this research.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Cardiac & Cardiovascular Systems
Prachi Umbarkar, Sultan Tousif, Anand P. Singh, Joshua C. Anderson, Qinkun Zhang, Michelle D. Tallquist, James Woodgett, Hind Lal
Summary: This study reveals the important role of cardiac fibroblast-GSK-3 alpha in myocardial fibrosis and heart failure, and identifies the molecular mechanism underlying this role through fibroblast kinome mapping. The results suggest that GSK-3 alpha plays a critical role in fibroblast transformation and fibrotic remodeling, independently of the canonical TGF-beta 1-SMAD3 pathway.
CIRCULATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Kyuhee Park, Yoonkyoung Shin, Gyeongbeen Lee, Hwantae Park, Yongmun Choi
Summary: The small molecule dabrafenib has been identified to promote Schwann cell differentiation by inhibiting ERK phosphorylation and enhancing ErbB2 and Akt phosphorylation. However, MEK and ERK inhibitors have no effect on key transcription factor expression, while pharmacological inhibition of PI3K interferes with dabrafenib-induced differentiation. This suggests that the ErbB2-PI3K-Akt axis is essential for Schwann cell differentiation induced by dabrafenib in vitro.
Article
Nutrition & Dietetics
Jingya Lyu, Kensaku Fukunaga, Hitomi Imachi, Seisuke Sato, Toshihiro Kobayashi, Takanobu Saheki, Tomohiro Ibata, Takafumi Yoshimura, Hisakazu Iwama, Koji Murao
Summary: The study demonstrated that oxidized low-density lipoprotein (OxLDL) downregulates ABCA1 expression through the MEK/ERK/LXR pathway, leading to lipid accumulation in INS-1 cells, potentially resulting in impaired insulin synthesis and glucose-stimulated insulin secretion (GSIS).
Article
Biochemistry & Molecular Biology
Wei Liu, Lei Wang, Jiajia Zhang, Kun Cheng, Wenming Zheng, Zhenling Ma
Summary: Ovarian cancer has a lower incidence rate compared to other gynecological tumor types, but it has the second-highest death rate. CCL2, a multifunctional factor associated with cancer progression, was found to promote proliferation and metastasis of ovarian cancer cells when overexpressed. Knocking down CCL2 inhibited ovarian cancer cell proliferation, migration, and invasion. The study showed that MAP3K19 is the key target through which CCL2 regulates ovarian cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Thomas Yul Avery, Natalie Koehler, Robert Zeiser, Tilman Brummer, Dietrich Alexander Ruess
Summary: Hyperactivation of the RAS-RAF-MEK-ERK cascade plays a significant role in the oncogenesis of various tumors. It mediates the crosstalk between tumor, tumor microenvironment, and the immune system, leading to immune escape mechanisms and establishment of a tumor-supporting environment. Pharmacological interruption of this pathway disrupts tumor cells and modifies the tumor microenvironment, as well as anti-tumor immunomodulation. MEK inhibition has shown promise in modulating immune responses. However, the durable efficacy, therapy resistance, and toxicity still pose challenges for the clinical application of therapeutic agents targeting RAS-RAF-MEK-ERK hyperactivation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Shinsuke Fujii, Takuma Ishibashi, Megumi Kokura, Tatsufumi Fujimoto, Shinji Matsumoto, Satsuki Shidara, Kari J. Kurppa, Judith Pape, Javier Caton, Peter R. Morgan, Kristiina Heikinheimo, Akira Kikuchi, Eijiro Jimi, Tamotsu Kiyoshima
Summary: Ameloblastoma is a slow-growing odontogenic neoplasm with reported cases of successful treatment using a BRAF inhibitor. Recent research indicates a potential involvement of the MAPK pathway in Ameloblastoma development, with ARL4C expression possibly promoting tumorigenesis. Further investigation into the function of ARL4C in Ameloblastoma is needed.
JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chenyun Guo, Hao Xu, Yu Zhou, Zhihua Wu, Bin Jiang, Hanyu Chen, Donghai Lin
Summary: Cefotetan binds to hRKIP protein, relieving its inhibitory effect on the Ras/Raf1/MEK/ERK signaling pathway and enhancing ERK phosphorylation level. Several residues play a crucial role in the binding of hRKIP and Cefotetan. The binding of Cefotetan with hRKIP promotes protein motion, providing a basis for developing new drugs.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Koki Watanabe, Daiki Asano, Hiroko Ushikubo, Akane Morita, Asami Mori, Kenji Sakamoto, Kunio Ishii, Tsutomu Nakahara
Summary: Metformin can protect against NMDA-induced retinal neurotoxicity by activating the AMPK and MEK/ERK signaling pathways in rats. This neuroprotective effect may be partially due to inhibitory effects on inflammatory responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Weibo Liu, Teng Li, Wenhao Hu, Quanbo Ji, Fanqi Hu, Qi Wang, Xiaoqing Yang, Dengbin Qi, Hui Chen, Xuesong Zhang
Summary: HCK plays a crucial role in the tumorigenesis, progression, and metastasis of OS through the MEK/ERK pathway, suggesting it as a potential target for developing treatments for OS.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Yanlin Song, Zhenfei Bi, Yu Liu, Furong Qin, Yuquan Wei, Xiawei Wei
Summary: Molecular target inhibitors have been approved for tumor treatment and mainly target cell proliferation and metabolism. The RAS-RAF-MEK-ERK pathway plays essential roles in cell functions and abnormal activation of this pathway leads to tumor development. In this review, the development and potential combinations of inhibitors targeting this pathway are discussed.
Article
Chemistry, Medicinal
Aarion Romany, Ruibin Liu, Shaoqi Zhan, Joseph Clayton, Jana Shen
Summary: The ERK pathway is crucial in tumorigenesis and there is a need for novel covalent inhibitors due to limited efficacy of current noncovalent inhibitors approved by FDA. A systematic study revealed possible targets for the development of covalent inhibitors against ERK pathway kinases.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Chuntian Huang, Ruijuan Du, Xuechao Jia, Kangdong Liu, Yan Qiao, Qiong Wu, Ning Yao, Lu Yang, Liting Zhou, Xuejiao Liu, Pu Xiang, Mingxia Xin, Yan Wang, Xiaojie Chen, Dong Joon Kim, Zigang Dong, Xiang Li
Summary: The study revealed that CDK15 plays a pivotal role in colorectal cancer progression by phosphorylating PAK4 to promote tumor growth. The CDK15-PAK4 axis may serve as a novel therapeutic target for colorectal cancer.
CELL DEATH AND DIFFERENTIATION
(2022)
Review
Endocrinology & Metabolism
Diane M. Duffy, CheMyong Ko, Misung Jo, Mats Brannstrom, Thomas E. Curry
Article
Immunology
Harvinder Talwar, Mohamad Bouhamdan, Christian Bauerfeld, T. Jaya Talreja, Rifdat Aoidi, Nicolas Houde, Jean Charron, Lobelia Samavati
JOURNAL OF IMMUNOLOGY
(2019)
Article
Reproductive Biology
Chan Jin Park, Radwa Barakat, Alexander Ulanov, Zhong Li, Po-Ching Lin, Karen Chiu, Sherry Zhou, Pablo Perez, Jungyeon Lee, Jodi Flaws, ChemYong Jay Ko
REPRODUCTIVE TOXICOLOGY
(2019)
Article
Environmental Sciences
Radwa Barakat, Talia Seymore, Po-Ching Patrick Lin, Chan Jin Park, CheMyong Jay Ko
ENVIRONMENTAL RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Do-Hyun Kim, Hong-Jai Park, Hyeon-Soo Park, Jae-Ung Lee, CheMyong Ko, Myung Chan Gye, Je-Min Choi
EXPERIMENTAL AND MOLECULAR MEDICINE
(2019)
Article
Cell Biology
Chan Jin Park, Po-Ching Lin, Sherry Zhou, Radwa Barakat, Shah Tauseef Bashir, Jeong Moon Choi, Joseph A. Cacioppo, Oliver R. Oakley, Diane M. Duffy, John P. Lydon, CheMyong J. Ko
Article
Oncology
Hongguang Wu, Dan He, Soma Biswas, Md Shafiquzzaman, Xin Zhou, Jean Charron, Yibin Wang, Bijaya K. Nayak, Samy L. Habib, Huijuan Liu, Baojie Li
Summary: Activation of the mTOR signaling pathway combined with inactivation of the p38MAPK-p53/p16 axis initiates the development of RCC from renal proximal tubules, uncovering previously unidentified mechanisms and potential therapeutic targets for RCC treatment.
Article
Endocrinology & Metabolism
Yoshiko Matsumoto Ikushima, Motoharu Awazawa, Naoki Kobayashi, Sho Osonoi, Seiichi Takemiya, Hiroshi Kobayashi, Hirotsugu Suwanai, Yuichi Morimoto, Kotaro Soeda, Jun Adachi, Masafumi Muratani, Jean Charron, Hiroki Mizukami, Noriko Takahashi, Kohjiro Ueki
Summary: Research has shown that decreased phosphorylation of ERK1/2 in diabetes pathology leads to beta-cell dysfunction and hyperglycemia. Abrogation of ERK signaling in pancreatic beta-cells through deletion of Mek1 and Mek2 results in insufficient insulin production, reduced beta-cell proliferation, and decreased insulin exocytosis events in individual beta-cells.
Article
Cell Biology
Ke Li, Hongguang Wu, Ao Wang, Jean Charron, Yuji Mishina, Samy L. Habib, Huijuan Liu, Baojie Li
Summary: The activation of mTOR can promote proliferation and inhibit differentiation of gastric epithelial progenitors. Through regulating MEK1-ERKs and BMP-Smad1 pathways, mTOR signaling controls the homeostasis and cancerization of Lgr5(+) GEPs in gastric tissues.
Article
Cell Biology
Laurent Beuret, Simon-Pierre Fortier-Beaulieu, Vincent Rondeau, Sophie Roy, Nicolas Houde, Karl Balabanian, Marion Espeli, Jean Charron
Summary: Studies have highlighted the crucial role of Mek genes in hematopoietic cell proliferation and differentiation, with functional ablation leading to anemia and other hematopoietic abnormalities. However, mice retaining one functional Mek gene allele did not exhibit significant defects in erythropoiesis, suggesting a certain level of redundancy among Mek genes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ke-Qin Gong, Carmen Mikacenic, Matthew E. Long, Charles W. Frevert, Timothy P. Birkland, Jean Charron, Sina A. Gharib, Anne M. Manicone
Summary: Inhibition of MAP2K2 can improve acute lung injury (ALI) and deficiency of MAP2K2 can accelerate the resolution of ALI. Genetic variants in MAP2K2 are associated with mortality from acute respiratory distress syndrome (ARDS). MAP2K2 plays an important role in promoting and sustaining proinflammatory pathway activation in ALI.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Nicolas Houde, Laurent Beuret, Amelie Bonaud, Simon-Pierre Fortier-Beaulieu, Kim Truchon-Landry, Rifdat Aoidi, Emilie Pic, Nagham Alouche, Vincent Rondeau, Geraldine Schlecht-Louf, Karl Balabanian, Marion Espeli, Jean Charron
Summary: This study reveals the critical role of fine-tuning the ERK/MAPK pathway in immune cell activation and function. It also demonstrates that MEK1 and MEK2 isoforms play distinct roles in lymphocyte activation and disease development.
Article
Medicine, Research & Experimental
Matthew E. Long, Ke-Qin Gong, William E. Eddy, Joseph S. Volk, Eric D. Morrell, Carmen Mikacenic, T. Eoin West, Shawn J. Skerrett, Jean Charron, W. Conrad Liles, Anne M. Manicone
Meeting Abstract
Cardiac & Cardiovascular Systems
Elizabeth Sawicki, Radwa Barakat, Benjamin Lew, Kevin Kim, CheMyong Ko, Hyungsoo Choi
Article
Endocrinology & Metabolism
Somang Lee-Thacker, Yohan Choi, Ichiro Taniuchi, Takeshi Takarada, Yukio Yoneda, CheMyong Ko, Misung Jo