Article
Cell Biology
Yu Zhang, Moises Hernandez, Jonathan Gower, Nolan Winicki, Xena Morataya, Sebastian Alvarez, Jason X-J Yuan, John Shyy, Patricia A. Thistlethwaite
Summary: This study found that the NOTCH3 pathway plays a crucial role in controlling vascular smooth muscle cell proliferation and differentiation in the pulmonary arterial tree. In pulmonary arterial hypertension (PAH) patients, JAGGED-1 is overexpressed in small pulmonary artery smooth muscle cells and selectively activates NOTCH3 signaling, leading to increased cellular proliferation. On the other hand, DELTA-LIKE 4 inhibits NOTCH3 signaling and retards smooth muscle cell proliferation. A new monoclonal antibody was developed to block JAGGED-1-induced cleavage of NOTCH3 and successfully reversed pulmonary hypertension in animal models without toxic side effects. Targeting JAGGED-1 activation of NOTCH3 may be an effective and safe strategy for treating PAH.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Cell & Tissue Engineering
Young-Woo Jo, Inkuk Park, Kyusang Yoo, Hyun-Young Woo, Ye Lynne Kim, Yea-Eun Kim, Ji-Hoon Kim, Young-Yun Kong
Summary: This study found that Notch1 and Notch2 play distinct roles in maintaining the population of myogenic progenitors (MPs) during fetal myogenesis, with Notch1 inducing cell cycle exit and Notch2 suppressing premature differentiation. The activation of Notch1 and Notch2 signaling in MPs is also shown to be distinctively regulated by interactions with Notch ligand-expressing myofibers and MP-lineage cells, respectively.
Article
Immunology
Yonglin Chen, Manxue Jia, Sharon Wang, Sherry Xu, Nanhai He
Summary: The TNFR2 blocking antibody AN3025 can enhance anti-tumor immune response, inhibit Tregs-mediated immunosuppression, and suppress tumor growth by targeting TNFR2 expression on Tregs in the tumor microenvironment. Its potent anti-tumor efficacy as a monotherapy or in combination with anti-PD-1 antibody supports further clinical development for various human tumors.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Frederick Allen, Ivan Maillard
Summary: The Notch signaling pathway has been investigated as a therapeutic target for cancers and immune/inflammatory disorders, orchestrating cell fate decisions and regulating immune responses through cell-to-cell contacts. It has shown potential in inhibiting tumor growth and preventing/reversing inflammatory disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Luigi Borzacchiello, Roberta Veglia Tranchese, Roberta Grillo, Roberta Arpino, Laura Mosca, Giovanna Cacciapuoti, Marina Porcelli
Summary: Recent research has found a correlation between dysregulated Notch and tumor metastasis in colorectal cancer (CRC). The study also showed that S-adenosyl-L-methionine (AdoMet) could act as a potential antimetastatic agent by modulating the expression of miRNA-34a/-34c/-449a and inhibiting the migration of CRC cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Yaser Peymanfar, Yu-Wen Su, Mohammadhossein Hassanshahi, Cory J. Xian
Summary: This study reveals that intensive cancer chemotherapy with methotrexate (MTX) can lead to dysfunction and damage of bone vasculature. The activation of Notch2 signaling pathway and increased production of inflammatory cytokine TNF alpha are associated with the impairment of micro-vasculature caused by MTX treatment. Blockade of Notch2 can alleviate the adverse effects on bone micro-vasculature and protect endothelial cell functions from MTX damage.
Article
Oncology
Hayley M. Sabol, Tania Amorim, Cody Ashby, David Halladay, Judith Anderson, Meloney Cregor, Megan Sweet, Intawat Nookaew, Noriyoshi Kurihara, G. David Roodman, Teresita Bellido, Jesus Delgado-Calle
Summary: In multiple myeloma, Notch3 signaling plays a crucial role in promoting tumor growth and bone destruction. Inhibiting Notch3 can reduce MM cell proliferation and decrease their osteoclastogenic potential. Notch3 acts as a mediator of cell communication between multiple myeloma cells and osteocytes.
Article
Medicine, Research & Experimental
Wenyan Fu, Guangyao Li, Changhai Lei, Kewen Qian, Shuyi Zhang, Jian Zhao, Shi Hu
Summary: PARP inhibitors are used in treating BRCA-mutant cancers. Combining bispecific antibodies targeting both EGFR and Notch signalling can decrease the enrichment of stem-like cells, delay the development of acquired resistance, and have a more substantial antitumour effect.
Article
Biochemistry & Molecular Biology
Michael Powers, Liu Liu, Dane Deemer, Selina Chen, Aaron Scholl, Masafumi Yoshinaga, Zijuan Liu
Summary: Selenium is an essential micronutrient in mammals and selenite is used to alleviate deficiency symptoms and potentially serve as a chemotherapeutic agent. This study identified selenite as a novel inhibitor of Delta-Notch signaling, showing potential in treating diseases like cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Zhibao Wang, Bo Cao, Peng Ji, Fan Yao
Summary: Propofol inhibits tubular structure formation and various biological functions of tumor-associated endothelial cells, including migration, adhesion, proliferation, and survival, by suppressing the expression and secretion of multiple pro-angiogenic factors and specific signaling pathways. These findings provide preclinical evidence for the anti-cancer properties of propofol and its potential mechanisms in inhibiting tumor growth and metastasis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Immunology
Hongxin Wang, Yushe Wang, Yong Wang
Summary: miR-222-3p inhibits the formation of MB stem-like cells via the Notch2/c-myc pathway, while altering cell cycle distribution and cell viability.
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
(2022)
Article
Environmental Sciences
Yong Wang, Wen Li, Fangmei Huang, Xiaojian Wu, Wenbin Chen, Ming Dong, Jie Zhou
Summary: The study demonstrates that SCA inhibits the proliferation of myeloma cells by promoting pro-apoptotic proteins and targeting the expression of Notch3. This suggests that SCA may have potential for further development as a treatment for multiple myeloma.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Oncology
Kai Huang, Wenwu Luo, Jinmei Fang, Changjun Yu, Guangjie Liu, Xiaodong Yuan, Yun Liu, Wenyong Wu
Summary: Our study found that Notch3 is highly expressed in colon tumor tissues and regulates the infiltration of macrophages. The expression of Notch3 is positively correlated with macrophage recruitment-related cytokines in colon tumor tissues. Depletion of Notch3 attenuated colon cancer tumor growth and reduced infiltration of immunosuppressive cells in the tumor microenvironment.
Review
Biochemistry & Molecular Biology
Antonino B. D'Assoro, Roberto Leon-Ferre, Eike-Benjamin Braune, Urban Lendahl
Summary: The Notch signaling pathway is important for normal development, but dysregulation of this pathway is associated with various types of tumors. In addition to its role in tumor cells, Notch signaling also affects non-mutated cells in the tumor microenvironment and their interactions with tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Jingchao Bai, Bowen Ding, Hui Li
Summary: TNF receptor 2 (TNFR2) has emerged as a promising immune checkpoint target in cancer treatment due to its crucial role in tumor microenvironments. Blocking or activating TNFR2 may offer potential therapeutic strategies, with evidence suggesting that TNFR2 activation can also inhibit tumor progression.
FRONTIERS IN IMMUNOLOGY
(2022)