Article
Cardiac & Cardiovascular Systems
Chan Soon Park, Soo Hyun Kim, Hae Young Yang, Ju-Hee Kim, Ralph Theo Schermuly, Ye Seul Cho, Hyejeong Kang, Jae-Hyeong Park, Eunhyeong Lee, HyeonJin Park, Jee Myung Yang, Tae Wook Noh, Seung-Pyo Lee, Sun Sik Bae, Jinju Han, Young Seok Ju, Jun-Bean Park, Injune Kim
Summary: The loss of Sox17 contributes to the development of PAH. Abnormal pathological features were observed in pulmonary endothelial cells in both animal models and PAH patients. A potential therapeutic target for PAH treatment was identified.
CIRCULATION RESEARCH
(2022)
Article
Oncology
Chiara Modica, Marco Cortese, Francesca Bersani, Andrea Maria Lombardi, Francesca Napoli, Luisella Righi, Riccardo Taulli, Cristina Basilico, Elisa Vigna
Summary: The MET receptor and its ligand Hepatocyte Growth Factor (HGF) play important roles in cell proliferation, survival, motility, and invasion. The HGF/MET axis regulates both cell-autonomous and non-cell-autonomous functions in cancer cell dissemination. Knocking out the MET gene in cancer cells allowed for the evaluation of the role of the HGF/MET axis in cell-autonomous functions independently of its effect on tumor microenvironment cells. The results suggest a crucial contribution of the HGF/MET axis in driving the metastatic process.
Article
Immunology
Mahdia Benkhoucha, Ngoc Lan Tran, Gautier Breville, Isis Senoner, Paul F. Bradfield, Thalia Papayannopoulou, Doron Merkler, Thomas Korn, Patrice H. Lalive
Summary: CD4(+)c-Met(+) T cells are increased in multiple sclerosis models and exhibit a pro-inflammatory phenotype with enhanced adhesion and migration.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Pharmacology & Pharmacy
Yang Zhao, Wenling Ye, Yan-Dong Wang, Wei-Dong Chen
Summary: Hepatocyte growth factor (HGF) is a multifunctional cytokine that regulates cell growth, proliferation, and survival by activating the c-Met signaling pathway, and it plays a crucial role in liver regeneration.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Chiara Modica, Martina Olivero, Francesca Zuppini, Melissa Milan, Cristina Basilico, Elisa Vigna
Summary: This study explores the molecular mechanisms of the MET/HGF signaling pathway in the interaction between pancreatic cancer cells and the tumor microenvironment. Through large-scale gene expression analysis, tenascin C was identified as a key gene involved in sustaining the malignant phenotype. Further research demonstrates the modulation of tenascin C by MET activation, suggesting a role in tumor-stroma interplay during pancreatic tumor progression.
Review
Oncology
Ryota Tanaka, Mizue Terai, Eric Londin, Takami Sato
Summary: The HGF/MET signaling pathway is crucial in metastatic formation and treatment resistance in uveal melanoma, promoting tumorigenesis, tumor progression, and affecting cell survival, proliferation, motility, and migration. MET expression in metastatic uveal melanoma is associated with poor prognosis, with the pathway being a major mechanism of treatment resistance.
Article
Oncology
Patricia Dias Carvalho, Flavia Martins, Susana Mendonca, Andreia Ribeiro, Ana Luisa Machado, Joana Carvalho, Maria Jose Oliveira, Sergia Velho
Summary: This study reveals the role of mutant KRAS in modulating cell fate through autonomous and nonautonomous signaling mechanisms in colorectal cancer cells. Mutant KRAS autonomously controls processes such as proliferation and cell-cell aggregation, while cancer cell invasion depends on the cooperation between fibroblast-derived HGF and mutant KRAS regulation of C-MET expression.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Makoto Nishio, Terufumi Kato, Ryo Toyozawa, Toyoaki Hida
Summary: MET inhibitors used in the treatment of non-small cell lung cancer may cause peripheral edema, with potential mechanisms including disruption of vascular endothelial permeability balance and effects on renal function. Thorough assessment is needed to determine the underlying cause of edema, as it is common in cancer patients and may have similar symptoms to other conditions. Patients should be informed about the possibility of developing peripheral edema and evaluated before treatment initiation. Management options for edema include compression stockings, specific exercises, massage, limb elevation, and/or diuretic treatment.
Review
Oncology
Fatemeh Moosavi, Elisa Giovannetti, Godefridus J. Peters, Omidreza Firuzi
Summary: MET receptor is a promising therapeutic target in various human cancers, with HGF/MET combination therapies showing potential in overcoming drug resistance, targeting tumor microenvironment, and modulating drug metabolism. Further research is needed to fully understand the molecular mechanisms underlying successful pharmacological combinations.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Review
Cell Biology
Justas Stanislovas, Stephanie Kermorgant
Summary: This article discusses the cooperation between c-Met and several integrins, particularly beta 1 and beta 4, in various cell models. The study found that c-Met and integrins can cooperate through inside-out or outside-in signaling, promoting cell migration and invasion. In addition, integrins can act as signaling adaptors for c-Met, independent of their adhesive function, leading to anchorage-independent survival.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rishav Sharma, Rishabha Malviya
Summary: Pancreatic cancer is highly lethal and difficult to treat, with hypoxia promoting its development and spread. The interaction between cancer cells, stromal cells, and pancreatic stellate cells mediated by the HGF/c-MET pathway plays a crucial role in disease progression. Hypoxia and HGF/c-MET expression are important factors in pancreatic cancer treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Oncology
Soichiro Mori, Hirofumi Akita, Shogo Kobayashi, Yoshifumi Iwagami, Daisaku Yamada, Yoshito Tomimaru, Takehiro Noda, Kunihito Gotoh, Yutaka Takeda, Masahiro Tanemura, Yuichiro Doki, Hidetoshi Eguchi
Summary: Radiation therapy can induce increased c-Met expression in pancreatic cancer cells, leading to enhanced invasion and migration ability, promoting the risk of distant metastasis. Inhibiting c-Met can reverse this enhanced malignant potential.
Article
Oncology
Baiyao Wang, Wei Liu, Chunshan Liu, Kunpeng Du, Zhaoze Guo, Guoqian Zhang, Zhong Huang, Shuhui Lin, Bohong Cen, Yunhong Tian, Yawei Yuan, Junguo Bu
Summary: This study investigated the role of cancer-associated fibroblasts (CAFs) in the radiosensitivity of breast cancer cells. The researchers found that CAFs secrete HGF to activate the c-Met signaling pathway, promoting epithelial-to-mesenchymal transition, growth, and radioresistance of breast cancer cells. Radiation was also observed to enhance HGF secretion by CAFs and increase c-Met expression in breast cancer cells, leading to the activation of the HGF/c-Met signaling pathway.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Article
Oncology
Jacquelyn T. T. Saunders, Sunil Kumar, Angelica Benavides-Serrato, Brent Holmes, Kennedy E. E. Benavides, Muhammad T. T. Bashir, Robert N. N. Nishimura, Joseph Gera
Summary: A circular RNA encoded HGF protein variant, C-HGF, was discovered to activate c-MET and promote glioblastoma growth and invasion. Inhibition of C-HGF may provide a promising approach for glioblastoma treatment.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Miron Tokarski, Aneta Cierzniak, Dagmara Baczynska
Summary: This study investigates the effect of chemically-induced hypoxia on the expression of miRNA molecules in human endothelial cells and identifies several miRNAs that may affect the HGFA-HGF-c-Met signaling pathway. The findings shed new light on the role of miRNAs in hypoxia and highlight the importance of specific miRNAs in regulating this signaling pathway.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Biophysics
Yuichi Ogawa, Shojiro Kikuchi, Yoshihisa Yamashige, Keiichiro Shiraga, Takeshi Mitsunaka
Summary: This study monitored the growth of Escherichia coli using a CMOS near-field sensor array, successfully distinguishing between viable and heat-treated dead E. coli, and observing the suppression of growth by streptomycin. The results suggest that viable E. coli can be rapidly confirmed by changes in permittivity near the sensor surface caused by displacement of media by the bacteria.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Multidisciplinary Sciences
Emiko Mihara, Satoshi Watanabe, Nasir K. Bashiruddin, Nozomi Nakamura, Kyoko Matoba, Yumi Sano, Rumit Maini, Yizhen Yin, Katsuya Sakai, Takao Arimori, Kunio Matsumoto, Hiroaki Suga, Junichi Takagi
Summary: The RaPID system enables rapid discovery of small macrocyclic peptides binding desired targets. The lasso-grafting method proposed here involves implanting RaPID-derived peptides onto diverse proteins while maintaining both the cyclic peptide's binding properties and the host protein function.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Kentaro Kajiwara, Shotaro Yamano, Kazuhiro Aoki, Daisuke Okuzaki, Kunio Matsumoto, Masato Okada
Summary: CDCP1 promotes compensatory renal growth induced by HGF by integrating Src and Met signaling, playing a crucial role in this process.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biochemistry & Molecular Biology
Yumiko Tahira, Katsuya Sakai, Hiroki Sato, Ryu Imamura, Kunio Matsumoto
Summary: The researchers found that the residues N127, V140, and K144 at the NK1 dimer interface play important roles in Met activation by HGF. Mutant NK1 proteins with alanine replacements at these residues lost their ability to activate Met, while mutant HGF proteins with the same replacements retained their activity, suggesting a distinction in the structural basis for NK1-dependent Met dimer formation and HGF-dependent Met activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Atsushi Saitou, Yoshihiro Hasegawa, Naoki Fujitani, Shigeru Ariki, Yasuaki Uehara, Ukichiro Hashimoto, Atsushi Saito, Koji Kuronuma, Kunio Matsumoto, Hirofumi Chiba, Motoko Takahashi
Summary: The MET receptor is associated with resistance to tyrosine kinase inhibitors in non-small cell lung cancer. This study explores the roles of N-glycans in the proteolytic processing of MET and HGF-induced MET signaling. The findings suggest that N-glycans of MET affect the status and function of the receptor in a site-specific manner.
Review
Biochemistry & Molecular Biology
Masato Yoshihara, Shigehiko Mizutani, Yukio Kato, Kunio Matsumoto, Eita Mizutani, Hidesuke Mizutani, Hiroki Fujimoto, Satoko Osuka, Hiroaki Kajiyama
Summary: Blastocyst implantation involves crucial interactions between fibronectin in blastocysts and endometrial epithelial cells, with extracellular vesicles proposed as a new insight into facilitating this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Tetsuya Matsukawa, Shigehiko Mizutani, Kunio Matsumoto, Yukio Kato, Masato Yoshihara, Hiroaki Kajiyama, Kiyosumi Shibata
Summary: A higher activity of P-LAP was found in the urine of ovarian cancer patients compared to patients with benign or borderline malignant tumors. A cut-off value of 11.00 U/L for P-LAP showed a sensitivity of 77.8% and a specificity of 95.5% in distinguishing invasive cancer.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Yamato Komatsu, Naohiro Terasaka, Katsuya Sakai, Emiko Mihara, Risa Wakabayashi, Kunio Matsumoto, Donald Hilvert, Junichi Takagi, Hiroaki Suga
Summary: Lasso-grafting (LG) technology involves genetically implanting macrocyclic peptide pharmacophores into loops of arbitrary protein scaffolds to generate novel biologics. In this study, a neo-capsid that potently binds the hepatocyte growth factor receptor MET was created using this technology. This work demonstrates the potential of LG technology in generating capsid-based neobiologics capable of activating signaling receptors.
Article
Biochemistry & Molecular Biology
Suguru Kasai, Naomi Kuwayama, Yoshiharu Motoo, Atsuhiro Kawashima, Kunio Matsumoto, Seiji Yano, Kouji Matsushima, Kazuo Yasumoto
Summary: This study investigates the role of MET and VEGFR2 signaling pathways in the development of peritoneal carcinomatosis with malignant ascites in scirrhous gastric cancer. The dual inhibition of MET and VEGFR2 by Cabozantinib effectively inhibits the proliferation of cancer cells and ascites formation, prolongs the survival of mice, and shows potential as a therapeutic option for peritoneal carcinomatosis in scirrhous gastric cancer.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Naoyuki Kawase, Atsuya Sugihara, Kentaro Kajiwara, Michio Hiroshima, Kanako Akamatsu, Shigeyuki Nada, Kunio Matsumoto, Masahiro Ueda, Masato Okada
Summary: The CDCP1-SRC-ARHGEF7-RAC1 pathway plays a crucial role in HGF-induced invasion of a subset of breast cancer cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Kyoko Kamoshita, Kiyo-aki Ishii, Yumiko Tahira, Akihiro Kikuchi, Halimulati Abuduwaili, Natsumi Tajima-Shirasaki, Qifang Li, Hiroaki Takayama, Kunio Matsumoto, Toshinari Takamura
Summary: Insulin activates proteasome function by inhibiting protein ubiquitination through USP14, providing protection in hepatic cells. This study sheds light on the activation mechanism of USP14 and its pleiotropic effects, offering potential therapeutic strategies for obesity-related metabolic disorders.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Engineering, Biomedical
Katsuya Sakai, Nozomi Sugano-Nakamura, Emiko Mihara, Nichole Marcela Rojas-Chaverra, Sayako Watanabe, Hiroki Sato, Ryu Imamura, Dominic Chih-Cheng Voon, Itsuki Sakai, Chihiro Yamasaki, Chise Tateno, Mikihiro Shibata, Hiroaki Suga, Junichi Takagi, Kunio Matsumoto
Summary: The study shows that genetically grafting macrocyclic peptide pharmacophores into the structural loops of the Fc region of a human immunoglobulin can generate surrogate receptor agonists with longer half-lives in circulation and enhanced transport rates across the blood-brain barrier. This lasso-grafting approach allows for the development of protein therapeutics with improved stability and pharmacokinetics.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Medicine, Research & Experimental
Shota Warashina, Hiroki Sato, Maki Zouda, Maiko Takahashi, Yasuhiro Wada, Toby Passioura, Hiroaki Suga, Yasuyoshi Watanabe, Kunio Matsumoto, Hidefumi Mukai
Summary: In this study, Cu-64-labeled HiP-8 molecules were synthesized and used as PET probes in human HGF knock-in humanized mice. The results showed that Cu-64-labeled HiP-8 probes are suitable for tcHGF imaging in vivo, and secretory proteins like tcHGF can be a target for PET imaging.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Naoya Kawakami, Hiroki Sato, Naohiro Terasaka, Kunio Matsumoto, Hiroaki Suga
Summary: The researchers have developed a ubiquitin-based protein ligand multimer, called U-bodies, as a surrogate agonist for the MET receptor. These U-body constructs have high binding affinity, thermal stability, and proteolytic stability. By assembling them into dimeric, tetrameric, and octameric structures, potent MET activation and cell proliferation-promoting activities are achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Ryu Imamura, Hiroki Sato, Dominic Chih- Cheng Voon, Takayoshi Shirasaki, Masao Honda, Makoto Kurachi, Katsuya Sakai, Kunio Matsumoto
Summary: Met in epithelial tissue plays a crucial role in cytokine production, and its tyrosine kinase activity is not required for this process. The interaction between the intracellular carboxy terminus of Met and MAVS in RLR-mediated signaling promotes immune responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
