Article
Multidisciplinary Sciences
Yoshitaka Kase, Tsukika Sato, Yuji Okano, Hideyuki Okano
Summary: The GADD45G gene promotes neurite outgrowth in human neurons by facilitating microtubule polymerization through the p38 MAPK/CDC25B signaling pathway. It is highly expressed in developing human cerebral specimens.
Article
Multidisciplinary Sciences
Maria Brooun, Willi Salvenmoser, Catherine Dana, Marius Sudol, Robert Steele, Bert Hobmayer, Helen McNeill
Summary: This study reveals the role of the Hippo pathway in regulating axis formation in cnidarian Hydra, suggesting its importance in early metazoan evolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Jiaqi Jin, Lei Zhang, Xueying Li, Weizhi Xu, Siyuan Yang, Jiagui Song, Wenhao Zhang, Jun Zhan, Jianyuan Luo, Hongquan Zhang
Summary: This study reveals that oxidative stress promotes acetylation of MOB1, a key component of the Hippo pathway, by inhibiting the degradation of acetyltransferase CBP. Acetylated MOB1 activates the Hippo pathway and serves as a better predictor for overall survival in patients with non-small cell lung cancer.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Christina Priest, Rohith T. Nagari, Lara Bideyan, Stephen D. Lee, Alexander Nguyen, Xu Xiao, Peter Tontonoz
Summary: The study illustrates the role of BRAP in modulating the hepatic Hippo pathway by regulating MST2, impacting liver cell morphology and turnover. Loss of BRAP leads to significant morphological changes in the liver, increased hepatocyte proliferation, cell death, and inflammation. The altered Hippo pathway signaling in Brap knockout mice affects liver lipid accumulation in dietary models of obesity, highlighting its relevance to human liver disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Soyeon Seo, Young A. Kim, Junekyoung Lee, Seunghwan Lee, Jumee Kim, Seunghee Lee
Summary: Fat3 plays a critical role in maintaining proper number of proliferating neural progenitors and regulating the expression of neural markers in the developing spinal cord.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Martina Di Rienzo, Alessandra Romagnoli, Fabiola Ciccosanti, Giulia Refolo, Veronica Consalvi, Giuseppe Arena, Enza Maria Valente, Mauro Piacentini, Gian Maria Fimia
Summary: The study revealed the critical role of AMBRA1 in controlling PINK1-PRKN mitophagy by interacting with ATAD3A and promoting PINK1 stability. This novel regulatory element may explain changes in PINK1 levels in neuropathological conditions.
Review
Oncology
Yi Xiao, Jixin Dong
Summary: The article emphasizes that cancer is increasingly viewed as a cell cycle disease, introducing the role of the Hippo pathway in cell cycle regulation, and discussing the impact of cell cycle dysregulation on cancer development.
Article
Multidisciplinary Sciences
Hirotoshi Soyama, Miki Nishio, Junji Otani, Toshiko Sakuma, Shintaro Takao, Shigeo Hara, Takaaki Masuda, Koshi Mimori, Shinya Toyokuni, John P. Lydon, Kazuwa Nakao, Hiroshi Nishina, Takumi Fukumoto, Tomohiko Maehama, Akira Suzuki
Summary: Breast cancer is the most common malignancy in women, and basal-like breast cancer (BLBC) is the most aggressive subtype. The Hippo-transcriptional coactivator with PDZ-binding motif (TAZ) pathway is found to be a key driver in the onset and progression of BLBC. Utilizing mouse models and human breast cancer cell lines, researchers have justified targeting the Hippo-TAZ pathway as a potential therapy for BLBC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Chenge Zhang, Yinhua Jin, Marco Marchetti, Mitchell R. Lewis, Omar T. Hammouda, Bruce A. Edgar
Summary: This study reveals that the transcriptional repressor Cic and its targets, pnt and Ets21C, are downstream effectors of mitogenic EGFR signaling in Drosophila intestinal stem cells. These factors promote metabolic changes that increase ISC mass, mitochondrial growth, and activity. The study also shows that Pnt and Ets21C directly upregulate genes involved in DNA replication, cell cycle, oxidative phosphorylation, TCA cycle, and fatty acid beta-oxidation. The work highlights the role of EGFR signaling in coordinating cell growth and division through alterations in metabolism.
Article
Cell Biology
Niall P. Quinn, Lucia Garcia-Gutierrez, Carolanne Doherty, Alexander von Kriegsheim, Emma Fallahi, David B. Sacks, David Matallanas
Summary: The scaffold protein IQGAP1 has been identified as a novel interactor of the core kinases MST2 and LATS1 in the Hippo pathway, suppressing their kinase activity and YAP1-dependent transcription. Additionally, it serves as a negative regulator of the non-canonical pro-apoptotic pathway and may facilitate crosstalk with the ERK and AKT signalling modules. Bile acids can regulate the IQGAP1-MST2-LATS1 signalling module in hepatocellular carcinoma cells, potentially inhibiting MST2-dependent apoptosis and hepatocyte transformation.
Article
Biochemistry & Molecular Biology
Kento Okamoto, Toshinori Ando, Hiroki Izumi, Susumu S. Kobayashi, Tomoaki Shintani, J. Silvio Gutkind, Souichi Yanamoto, Mutsumi Miyauchi, Mikihito Kajiya
Summary: The Hippo signaling pathway and its downstream effector YAP play a central role in cell proliferation. Dysregulation of the Hippo pathway triggers YAP hyperactivation, thereby inducing head and neck squamous cell carcinoma (HNSCC). Our findings suggest that co-targeting both AXL and EGFR represent a promising therapeutic approach in patients with EGFR-altered cancers.
Article
Cell Biology
Qiang Han, Xuezhu Rong, Xuyong Lin, Xiupeng Zhang, Chuifeng Fan, Huanyu Zhao, Enhua Wang
Summary: WBP2 is highly expressed in lung cancer and correlates with clinical features and prognosis. Functional experiments demonstrate that WBP2 promotes proliferation and invasion of lung cancer cells. WBP2 inhibits Hippo pathway activity by competitively binding to WWC3 and LATS1, leading to YAP nuclear translocation.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Jian Xiao, Yanni Xiong, Liu-Ting Yang, Ju-Qiong Wang, Zi-Mu Zhou, Le-Wei Dong, Xiong-Jie Shi, Xiaolu Zhao, Jie Luo, Bao-Liang Song
Summary: The study identifies POST1 as a crucial gene involved in the SREBP signaling pathway, promoting the generation of functional S1P-C'/C and regulating protein cleavage. POST1 plays important roles in maintaining lipid homeostasis, unfolded protein response, lipoprotein metabolism, and lysosome biogenesis.
Review
Biochemistry & Molecular Biology
Mohammad Reza Zinatizadeh, Seyed Rouhollah Miri, Peyman Kheirandish Zarandi, Ghanbar Mahmoodi Chalbatani, Catarina Raposo, Hamid Reza Mirzaei, Mohammad Esmaeil Akbari, Habibollah Mahmoodzadeh
Summary: Hippo tumor suppressor pathway regulates cell growth and affects tumor progression, with MST kinases activating AGC kinase dmWts or LATS effector, and YAP as a cofactor for transcription factors. Loss of Hippo pathway may have significant consequences on RAS-RAF mutations in cancer.
Article
Immunology
Xufeng Luo, Rui Zhang, Mengji Lu, Shi Liu, Hideo A. Baba, Guido Gerken, Heiner Wedemeyer, Ruth Broering
Summary: This study comprehensively investigated the molecular interactions between HBV-triggered TLR signaling and the Hippo pathway, revealing their important roles in immune regulation. Experimental results demonstrated that MyD88-dependent TLR signaling activates NF-kappa B and Hippo signaling, suggesting potential implications for novel HBV cure strategies that interfere with pathogen recognition receptors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nadia Arang, Simone Lubrano, Damiano Cosimo Rigiracciolo, Daniela Nachmanson, Scott M. Lippman, Prashant Mali, Olivier Harismendy, J. Silvio Gutkind
Summary: G proteins and G protein-coupled receptors activate signal transduction pathways that promote cell growth and survival. This study found that G alpha q promotes PI3K/AKT signaling pathway activation, leading to resistance to FAK inhibition. These findings establish a novel link between G alpha q-driven signaling and the stimulation of PI3K, demonstrating the aberrant activation of signaling networks underlying the growth and survival of UM and other G alpha q-driven malignancies.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Nurina Febriyanti Ayuningtyas, Chanbora Chea, Toshinori Ando, Karina Erda Saninggar, Keiji Tanimoto, Toshihiro Inubushi, Nako Maishi, Kyoko Hida, Masanobu Shindoh, Mutsumi Miyauchi, Takashi Takata
Summary: This study evaluated the inhibitory effects of bovine lactoferrin (bLF) on tumor angiogenesis in vivo and in vitro. The results showed that bLF inhibited proliferation, migration, and tube formation in tumor endothelial cells (TECs) while promoting apoptosis. This effect was achieved through the inhibition of p-p65 via binding with TNF receptor-associated factor 6 (TRAF6), leading to the down-regulation of hypoxia inducible factor-alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF), specifically in TECs.
Article
Dentistry, Oral Surgery & Medicine
Koichi Koizumi, Taishi Sakaue, Youji Nakase, Fumitaka Obayashi, Toshinori Ando, Tomoaki Shintani, Souichi Yanamoto
Summary: Multiple myeloma is a hematologic malignancy characterized by neoplastic proliferation of monoclonal plasma cells. This case report presents a rare occurrence of extramedullary disease in the submandibular region of multiple myeloma. The patient underwent surgical resection and has been successfully treated with chemotherapy for 1 year without recurrence.
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY
(2023)
Review
Dentistry, Oral Surgery & Medicine
Atsuko Hamada, Ryouji Tani, Naohiro Kimura, Yuki Taguchi, Suguru Hirota, Toshinori Ando, Kosei Okamoto, Shigeaki Toratani, Souichi Yanamoto
Summary: Salivary gland tumors are histologically diverse, and this report presents a rare case of primary secretory carcinoma of the minor salivary gland in the lip, with the ETV6-NTRK3 fusion gene. The patient underwent surgical treatment, and no recurrence or metastasis has been observed 13 months postoperatively.
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY
(2023)
Article
Oncology
Alison E. Smith, Stacia Chan, Zhiyong Wang, Asako Mccloskey, Quinn Reilly, Jayden Z. Wang, Hetika Vora Patel, Keiichi Koshizuka, Harris S. Soifer, Linda Kessler, Ashley Dayoub, Victoria Villaflor, Douglas R. Adkins, Justine Y. Bruce, Alan L. Ho, Cesar A. Perez, Glenn J. Hanna, Amaya Gasco Hernandez, Andrew Saunders, Stephen Dale, J. Silvio Gutkind, Francis Burrows, Shivani Malik
Summary: The outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) are poor, and there are limited treatment options for those who progress on standard-of-care immunotherapy. Researchers have developed a combination therapy targeting the key drivers of HNSCC, PI3K-mTOR and HRAS, using the inhibitors tipifarnib and alpelisib. This combination therapy has shown promise in preclinical studies and early clinical trials, with potential to benefit over 45% of patients with recurrent/metastatic HNSCC. Additionally, tipifarnib may enhance the effectiveness of other targeted therapies by preventing adaptive resistance.
Article
Oncology
Sankar Jagadeeshan, Manu Prasad, Mai Badarni, Talal Ben-Lulu, Vijayasteltar Belsamma Liju, Sooraj Mathukkada, Claire Saunders, Avital Beeri Shnerb, Jonathan Zorea, Ksenia M. Yegodayev, Monica Wainer, Liza Vtorov, Irit Allon, Ofir Cohen, Gro Gausdal, Dinorah Friedmann-Morvinski, Sok Ching Cheong, Alan L. Ho, Ari J. Rosenberg, Linda Kessler, Francis Burrows, Dexin Kong, Jennifer R. Grandis, J. Silvio Gutkind, Moshe Elkabets
Summary: The presence of mutated HRAS in head and neck cancer patients is associated with poor prognosis and high metastasis rate. Mutated HRAS promotes cancer cell invasion and metastasis by suppressing the Hippo pathway and promoting AXL expression. The use of tipifarnib, a farnesyltransferase inhibitor, can activate the Hippo pathway, suppress metastasis, and regulate angiogenesis in HNC.
Article
Biotechnology & Applied Microbiology
Shuo Wang, Zhi-Zhong Wu, Su-Wen Zhu, Shu-Cheng Wan, Meng-Jie Zhang, Bo-Xin Zhang, Qi-Chao Yang, Yao Xiao, Hao Li, Liang Mao, Zhi-Yong Wang, J. Silvio Gutkind, Zhi-Jun Sun
Summary: Immune checkpoint blockade (ICB) treatment is effective in oncology, but has limitations including low response rates and a lack of efficacy predictors. Gasdermin protein expression is associated with a favorable tumor immune microenvironment and prognosis in head and neck squamous cell carcinoma. CTLA-4 blockade treatment induces gasdermin-mediated pyroptosis of tumor cells, with gasdermin expression correlating with treatment effectiveness. CTLA-4 blockade activates CD8+ T cells and increases levels of IFN-g and TNF-a cytokines, triggering tumor cell pyroptosis and release of inflammatory substances and chemokines.
Article
Biochemistry & Molecular Biology
Natalie Hewitt, Ning Ma, Nadia Arang, Sarah A. Martin, Ajit Prakash, Jeffrey F. DiBerto, Kevin M. Knight, Soumadwip Ghosh, Reid H. J. Olsen, Bryan L. Roth, J. Silvio Gutkind, Nagarajan Vaidehi, Sharon L. Campbell, Henrik G. Dohlman
Summary: Heterotrimeric guanine nucleotide-binding proteins (G proteins) act as molecular switches for cellular growth and metabolism. Mutations in the glutamine residue critical for GTP hydrolysis in the G protein alpha subunit are common in uveal melanoma. Our study reveals that these mutations have functional diversity and contribute to G protein functions beyond GTP hydrolysis.
Article
Dentistry, Oral Surgery & Medicine
Tomoaki Shintani, Kouji Ohta, Toshinori Ando, Yasutaka Hayashido, Souichi Yanamoto, Mikihito Kajiya, Hideki Shiba
Summary: This study aimed to explore the efficacy and safety of zinc acetate hydrate (ZAH) in patients with hypozincemia-induced dysgeusia. The study found that ZAH treatment significantly increased serum zinc levels, improved gustatory sensitivity, and did not affect serum copper levels, making it more effective than polaprezinc (PPZ).
Article
Dentistry, Oral Surgery & Medicine
Tatsuya Akitomo, Yuria Asao, Yuko Iwamoto, Satoru Kusaka, Momoko Usuda, Mariko Kametani, Toshinori Ando, Shinnichi Sakamoto, Chieko Mitsuhata, Mikihito Kajiya, Katsuyuki Kozai, Ryota Nomura
Summary: A 4-year-and-11-month-old boy had three supernumerary teeth, which required surgical treatment and long-term follow-up. The first supernumerary tooth was extracted at 5 years and 5 months, followed by two more at 7 years and 7 months and 8 years and 2 months. Malocclusion may be caused by the supernumerary teeth, and surgical exposure was performed to facilitate the eruption of the permanent teeth.
Article
Oncology
Ana Ruiz-Saenz, Chloe E. Atreya, Changjun Wang, Bo Pan, Courtney A. Dreyer, Diede Brunen, Anirudh Prahallad, Denise P. Munoz, Dana J. Ramms, Valeria Burghi, Danislav S. Spassov, Eleanor Fewings, Yeonjoo C. Hwang, Cynthia Cowdrey, Christina Moelders, Cecilia Schwarzer, Denise M. Wolf, Byron Hann, Scott R. VandenBerg, Kevan Shokat, Mark M. Moasser, Rene Bernards, J. Silvio Gutkind, Laura J. van 't Veer, Jean-Philippe Coppe
Summary: Coppe and colleagues discover a resistance mechanism in BRAF(V600E) colorectal cancers that can be overcome with COX2 inhibitors. SRC kinases play a role in resistance to BRAF/EGFR-targeted therapy and can be effectively targeted in combination with BRAF and EGFR. Compensatory activation of SRC kinases is mediated by an autocrine prostaglandin E-2 loop, which can be blocked with COX2 inhibitors. Co-targeting COX2, BRAF, and EGFR promotes long-lasting suppression of tumor growth in patient-derived tumor xenograft models.
Article
Biochemistry & Molecular Biology
Valeria Burghi, Justine S. Paradis, Adam Officer, Sendi Rafael Adame-Garcia, Xingyu Wu, Edda S. F. Matthees, Benjamin Barsi-Rhyne, Dana J. Ramms, Lauren Clubb, Monica Acosta, Pablo Tamayo, Michel Bouvier, Asuka Inoue, Mark von Zastrow, Carsten Hoffmann, J. Silvio Gutkind
Summary: This study focuses on the role of beta-arrestins in G protein-coupled receptor (GPCR) signaling. It is found that while G proteins are essential for GPCR signaling, beta-arrestins play a more prominent role in signal compartmentalization and modulation of gene expression.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Svein Erik Moe, Fredrik A. Erland, Siren Fromreide, Stein Lybak, Marianne Brydoy, Harsh N. Dongre, Sophia M. Dhayalan, Daniela-Elena Costea, Olav K. Vintermyr, Hans Jorgen Aarstad
Summary: This study found an association between somatic TP53 mutations and the presence of human papillomavirus (HPV) in tumors of head and neck squamous cell carcinoma (HNSCC) patients. Only 2 of 44 HPV-positive patients had TP53 mutations, while 42 of 60 HPV-negative patients had TP53 mutations. Furthermore, in HPV-negative patients, a higher percentage of somatic TP53 mutations were found in the TP53 R72 polymorphism cohort compared to the TP53 P72 cohort.
Article
Cell & Tissue Engineering
Shin Morimoto, Mikihito Kajiya, Hiroki Yoshii, Mai Yoshino, Susumu Horikoshi, Souta Motoike, Tomoyuki Iwata, Kazuhisa Ouhara, Toshinori Ando, Tetsuya Yoshimoto, Tomoaki Shintani, Noriyoshi Mizuno
Summary: Three-dimensional clumps of MSCs/ECM complexes (C-MSCs) can be implanted without artificial scaffolds, and their cellular properties can be regulated in vitro. The study aimed to generate cartilaginous tissue covered with a mineralized bone collar-like structure from human C-MSCs by combining chondrogenic and osteogenic induction, showing potential for bone-regenerative cell therapy.
STEM CELL REVIEWS AND REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Mai Yoshino, Mikihito Kajiya, Hiroki Yoshii, Shin Morimoto, Susumu Horikoshi, Misako Tari, Tomoyuki Iwata, Kazuhisa Ouhara, Toshinori Ando, Tetsuya Yoshimoto, Tomoaki Shintani, Noriyoshi Mizuno
Summary: This study compares the biological properties of widely-used MSC spheroids and newly-developed C-MSCs, providing insights into the distinct features of each 3D cell culture method and their potential applications in MSC-based cell therapy.
APPLIED SCIENCES-BASEL
(2023)