Review
Oncology
Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Mohammad Taheri, Majid Samsami
Summary: The Sonic Hedgehog (Shh) signaling pathway plays a crucial role in tumor formation, resistance to conventional therapies, tissue regeneration, and neurodegenerative disorders. Numerous non-coding RNAs (ncRNAs) and miRNAs have been identified to interact with the Shh pathway in both malignant and non-malignant conditions. This review summarizes the interactions between ncRNAs and Shh in various contexts.
CANCER CELL INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Jun Wu, Rong Wang, Xuechun Kan, Jinghan Zhang, Wen Sun, David Goltzman, Dengshun Miao
Summary: This study reveals that the activation of the Shh-Gli-Bmi1 signaling pathway plays a critical role in the bone anabolic action induced by p27 deficiency. Bmi1 may be an important therapeutic target for treating osteoporosis caused by the activation of p27 signaling or inactivation of sonic hedgehog signaling.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Review
Cell Biology
Florian Hermans, Lara Hemeryck, Ivo Lambrichts, Annelies Bronckaers, Hugo Vankelecom
Summary: Tooth development relies on interactions between dental epithelium and mesenchyme, regulated by molecular pathways including Wnt, BMP, FGF, and Shh. These signaling modules intertwine during tooth development, outlining specific cell populations' development pathways.Recent studies have uncovered crucial Wnt-Shh interactions during odontogenesis, showing conservation in developing ectodermal appendages.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Po-Hsuan Su, Rui-Lan Huang, Hung-Cheng Lai, Lin-Yu Chen, Yu-Chun Weng, Chih-Chien Wang, Chia-Chun Wu
Summary: NKX6-1 expression is associated with poor prognosis and malignant potential in LMS, enhancing tumor cell aggressiveness in vitro and promoting tumor growth in vivo. Overexpression and knockdown of NKX6-1 affect stem cell transcription factors and signaling pathways, including the NOTCH and Sonic hedgehog pathways. Inhibition of the SHH pathway may be a potential therapeutic strategy for LMS patients with high expression of NKX6-1.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Ming-Rui Li, Xiu-Ju Luo, Jun Peng
Summary: Sonic hedgehog (SHH) signaling plays a crucial role in embryonic development, but its involvement in cardiac, cerebral, and vascular pathophysiology is still debated. Recent studies have shown that SHH signaling affects ion channels, which in turn influence the behavior of target cells in the cardio-cerebrovascular system. This article reviews the cascades of SHH signaling, explores its interaction with ion channels, and highlights the importance of studying its effect on ion homeostasis as a potential mechanism for cardio-cerebrovascular diseases.
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Vikas Daggubati, David R. Raleigh, Navdar Sever
Summary: This article discusses the role of the Hedgehog (Hh) family of lipid-modified signaling proteins in embryonic tissue patterning and postembryonic tissue homeostasis, as well as the involvement of dysregulated Hh signaling in familial and sporadic cancers. It also explores the binding and modulation of SMO activity by endogenous cholesterol and oxidized cholesterol derivatives. The article proposes models of sterol regulation of SMO and discusses the potential utility of steroidal SMO ligands or inhibitors of enzymes involved in sterol metabolism as cancer therapeutics.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Jun Sun, Dong Yeon Shin, Mark Eiseman, Alisha R. Yallowitz, Na Li, Sarfaraz Lalani, Zan Li, Michelle Cung, Seoyeon Bok, Shawon Debnath, Sofia Jenia Marquez, Tommy E. White, Abdul G. Khan, Ivo C. Lorenz, Jae-Hyuck Shim, Francis S. Lee, Ren Xu, Matthew B. Greenblatt
Summary: Slitrk5 acts as a negative regulator of hedgehog signaling in osteoblasts by enhancing osteoblast differentiation and inhibiting hedgehog signaling downstream targets. Mechanistically, Slitrk5 interacts with hedgehog ligands via its extracellular domain and with PTCH1 via its intracellular domain, ultimately modulating hedgehog signaling activity in the primary cilium.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Jangham Jung, Jaehun Kim, Tae-Lin Huh, Myungchull Rhee
Summary: TRIM46 is a RING finger E3 ligase that plays a role in neuronal polarity and axon specification. The zebrafish homologue trim46a is regulated by transcription factor Foxa2 and affects the development of the midbrain and MHB. Inhibition of SHH signaling pathway by cyclopamine leads to developmental defects in midbrain and MHB through trim46a regulation.
ANIMAL CELLS AND SYSTEMS
(2021)
Article
Medicine, Research & Experimental
Pingping Yu, Li Wang, Fanren Tang, Shuang Guo, Hongyan Liao, Cengceng Fan, Qin Yang
Summary: Resveratrol pretreatment promotes neurorestoration of ischemic cerebral injury through mediation of the Sonic Hedgehog signaling pathway, enhancing proliferation of neural stem cells.
Article
Multidisciplinary Sciences
Rachel K. Lex, Weiqiang Zhou, Zhicheng Ji, Kristin N. Falkenstein, Kaleigh E. Schuler, Kathryn E. Windsor, Joseph D. Kim, Hongkai Ji, Steven A. Vokes
Summary: The study challenges the current understanding that GLI3 repression is established before Hedgehog (HH) signaling and demonstrates that GLI3 is inert in the limb bud before HH onset. The loss of Gli3 does not increase target gene expression or accessibility, contrasting with post-HH signaling. GLI repression is established independently of HH signaling, but after its onset.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Jin Jiang
Summary: Cell-cell communication through evolutionarily conserved signaling pathways plays a crucial role in embryonic development and adult tissue homeostasis. The Hedgehog (Hh) pathway, originally discovered in Drosophila, has been found to be involved in human development and diseases. Abnormal activation of the Hh pathway is implicated in various human cancers. Studies from model organisms and human patients provide insights into the Hh signal transduction mechanisms and offer potential strategies for targeting this pathway in cancer treatment.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Yibin Pan, Jiena Zhou, Weidan Zhang, Lili Yan, Meifei Lu, Yongdong Dai, Hanjing Zhou, Songying Zhang, Jianhua Yang
Summary: The study found up-regulation of SHH and accumulation of SQSTM1/P62 in epithelial ovarian cancer. Cyp induced autophagy through the PI3K/AKT signaling pathway, and low-dose Cyp and chloroquine (CQ) significantly promoted the migratory ability of SKOV3 cells. The findings suggest that inhibition of the SHH pathway and autophagy may be a potential and effective therapy for the treatment of ovarian cancer.
Article
Biochemistry & Molecular Biology
Anna Hupfer, Anna Brichkina, Till Adhikary, Matthias Lauth
Summary: Medulloblastoma is the most common malignant brain tumor in children, with one subgroup driven by uncontrolled Hedgehog signaling. While clinically approved compounds exclusively target the transmembrane component Smoothened, drug resistance against SMO inhibitors is encountered frequently, highlighting the importance of identifying novel Hh pathway components.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Guangda Zheng, Juanxia Ren, Lu Shang, Yanju Bao
Summary: Pain is a complex physiological and psychological activity, and existing treatments for pain are not satisfactory. This article reviews the recent studies on the Sonic hedgehog (Shh) signaling pathway and its involvement in various pain-related diseases. Dysregulation of the Shh signaling pathway has been observed in conditions such as pancreatic cancer pain, bone cancer pain, chronic post-thoracotomy pain, degenerative lumbar disc disease, and toothache. Further research on the Shh signaling pathway may lead to new therapeutic options for pain management.
NEUROCHEMICAL RESEARCH
(2023)
Article
Plant Sciences
Yiqing Guan, Dongling Quan, Kai Chen, Liangqi Kang, Danni Yang, Huanxian Wu, Mengqiu Yan, Shaoyu Wu, Lin Lv, Guohua Zhang
Summary: The study investigates the effect of KAE therapy on extracellular matrix deposition and stimulation of EMT in vitro and in vivo. The results show that KAE can reduce blood pressure and decrease ECM components, TGF-01, and a-SMA in the kidneys of hypertension-induced rats with chronic kidney disease. In addition, KAE administration significantly suppresses proliferation, migration, and EMT in HK-2 cells treated with TGF-01.
Review
Cell Biology
Michiko Shirane, Hiroyuki Kamiguchi
Summary: Axon growth and guidance in the developing nervous system rely on intracellular membrane dynamics that involve endosome maturation and transport, as well as its regulated tethering to the endoplasmic reticulum (ER). Recent studies have identified several key molecules, such as protrudin, which plays a dynamic role at membrane contact sites between the ER and endosomes/lysosomes, and myosin Va, which acts as a sensor for ER-derived Ca2+ that triggers peri-ER membrane export. These molecules form different types of multiprotein complexes at the interface of organelles and, in response to their surrounding microenvironments, such as Ca2+ concentrations and lipid contents, regulate the directional movement of endosomal vesicles in extending axons. Here, we review the molecular mechanisms underlying membrane dynamics and inter-organelle interactions during neuronal morphogenesis.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Mitsuaki Fujimoto, Ryosuke Takii, Masaki Matsumoto, Mariko Okada, Keiich I. Nakayama, Ryuichiro Nakato, Katsunori Fujiki, Katsuhiko Shirahige, Akira Nakai
Summary: The study shows that phosphorylation of HSF1 during heat shock recruits histone acetyltransferases and histone acetylation reader proteins TRIM33 and TRIM24 to the HSP72 promoter, leading to histone H2B mono-ubiquitination, promoting the establishment of an active chromatin status, and affecting melanoma cell proliferation.
NATURE COMMUNICATIONS
(2022)
Article
Developmental Biology
Anna Lozano-Urena, Laura Lazaro-Carot, Esteban Jimenez-Villalba, Raquel Montalban-Loro, Isabel Mateos-White, Pere Duart-Abadia, Irene Martinez-Gurrea, Keiichi I. Nakayama, Isabel Farinas, Martina Kirstein, Cristina Gil-Sanz, Sacri R. Ferron
Summary: Adult neurogenesis relies on multipotent neural stem cells (NSCs) with unique properties and growth requirements. Although many imprinted genes' roles in adult neurogenesis are still unknown, insulin-like growth factor 2 (IGF2) has been shown to contribute to NSC maintenance and promote terminal differentiation into astrocytes, neurons, and oligodendrocytes. This differentiation effect is mediated by the expression of the maternally expressed gene Cdkn1c, encoding the cell cycle inhibitor p57, and occurs independently of its role in cell-cycle progression, balancing the relationship between astrogliogenesis, neurogenesis, and oligodendrogenesis.
Article
Biochemistry & Molecular Biology
Reona Wada, Shun Fujinuma, Hirokazu Nakatsumi, Masaki Matsumoto, Keiichi Nakayama
Summary: Mechanistic target of rapamycin complex 1 (mTORC1) is a serine-threonine kinase activated by extracellular signals, regulating various biological processes. PBX2 was identified as a novel target dephosphorylated downstream of mTORC1. The phosphorylation of PBX2 is regulated by the antagonistic actions of glycogen synthase kinase 3 (GSK3) and protein phosphatase 1 (PP1).
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Oncology
Akihiro Kitagawa, Tsuyoshi Osawa, Miwa Noda, Yuta Kobayashi, Sho Aki, Yusuke Nakano, Tomoko Saito, Dai Shimizu, Hisateru Komatsu, Maki Sugaya, Junichi Takahashi, Keisuke Kosai, Seiichiro Takao, Yushi Motomura, Kuniaki Sato, Qingjiang Hu, Atsushi Fujii, Hiroaki Wakiyama, Taro Tobo, Hiroki Uchida, Keishi Sugimachi, Kohei Shibata, Tohru Utsunomiya, Shogo Kobayashi, Hideshi Ishii, Takanori Hasegawa, Takaaki Masuda, Yusuke Matsui, Atsushi Niida, Tomoyoshi Soga, Yutaka Suzuki, Satoru Miyano, Hiroyuki Aburatani, Yuichiro Doki, Hidetoshi Eguchi, Masaki Mori, Keiichi I. Nakayama, Teppei Shimamura, Tatsuhiro Shibata, Koshi Mimori
Summary: This study analyzed the genomic, transcriptomic, proteomic, and metabolomic profiles of intrahepatic cholangiocarcinoma (ICC) samples, revealing the presence of multiple genomic alterations and metabolic pathway changes. The identified ICC-specific metabolic pathway could potentially be targeted for new therapeutic interventions.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Takeru Oka, Tsunaki Higa, Osamu Sugahara, Daisuke Koga, Shogo Nakayama, Keiichi I. Nakayama
Summary: This study established a syngeneic orthotopic transplantation model in mice based on intestinal cancer organoids, and revealed that quiescent p57(+) CSCs play a significant role in cancer relapse and are resistant to chemotherapy. Ablation of p57(+) CSCs suppressed tumor regrowth after chemotherapy, suggesting p57(+) CSCs as a promising therapeutic target for malignant intestinal cancer.
Article
Biochemistry & Molecular Biology
Yuki Kito, Akinobu Matsumoto, Kazuya Ichihara, Chisa Shiraishi, Ronghao Tang, Atsushi Hatano, Masaki Matsumoto, Peixun Han, Shintaro Iwasaki, Keiichi Nakayama
Summary: Translation begins with the binding of the eIF4F complex to the 5' mRNA cap, followed by scanning ribosomes searching for the start codon in the 5' untranslated region. This study shows that the ASC-1 complex (ASCC) associates with scanning ribosomes to regulate translation initiation. Knockdown of ASCC3, a subunit of ASCC, impairs the loading and scanning dynamics of the 43S preinitiation complex, leading to reduced translation efficiency. These findings demonstrate that ASCC not only promotes dissociation of colliding 80S ribosomes but also facilitates efficient translation initiation by scanning ribosomes.
Article
Cell Biology
Akira Kikuchi, Junichi Takagi, Shinji Takada, Tohru Ishitani, Yasuhiro Minami
Summary: Wnt2022 was an in-person meeting held in Awaji Yumebutai International Conference Center, Hyogo Prefecture, Japan, from November 15th to 19th, 2022, marking the first physical gathering in the past three years. The conference aimed to commemorate the 40th anniversary of Wnt research and discuss the future direction of this field, considering its crucial roles in various physiological and pathological processes. Despite travel and administrative restrictions due to COVID-19, the meeting successfully brought together 148 researchers from 21 countries, enabling face-to-face discussions.
Article
Multidisciplinary Sciences
Katsuhiko Takahashi, Hitoshi Amano, Tomohiko Urano, Minqi Li, Meiko Oki, Kazuhiro Aoki, Norio Amizuka, Keiichi I. Nakayama, Keiko Nakayama, Nobuyuki Udagawa, Nobuaki Higashi
Summary: The study found that p57(Kip2) plays an important role in bone development and is associated with the vitamin D receptor (VDR). 1,25-(OH)(2)VD3 can promote the differentiation of osteoblasts by regulating p57(Kip2), and simultaneously reduce the generation of osteoclasts.
Article
Multidisciplinary Sciences
Chisa Shiraishi, Akinobu Matsumoto, Kazuya Ichihara, Taishi Yamamoto, Takeshi Yokoyama, Taisuke Mizoo, Atsushi Hatano, Masaki Matsumoto, Yoshikazu Tanaka, Eriko Matsuura-Suzuki, Shintaro Iwasaki, Shouji Matsushima, Hiroyuki Tsutsui, Keiichi I. Nakayama
Summary: This study reveals that the RPL3L-encoded ribosomal protein specifically expressed in heart and skeletal muscle affects translation elongation dynamics, and its deficiency impairs cardiac contractility in mice. The results provide insights into the mechanisms and physiological relevance of tissue-specific translational regulation.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Shun Fujinuma, Hirokazu Nakatsumi, Hideyuki Shimizu, Shigeaki Sugiyama, Akihito Harada, Takeshi Goya, Masatake Tanaka, Motoyuki Kohjima, Masatomo Takahashi, Yoshihiro Izumi, Mikako Yagi, Dongchon Kang, Mari Kaneko, Mayo Shigeta, Takeshi Bamba, Yasuyuki Ohkawa, Keiichi I. Nakayama
Summary: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder that can lead to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). The transcription factor FOXK1 plays a key role in hepatic lipid metabolism by suppressing lipid catabolism. Inhibition of FOXK1 has shown promising results in improving hepatic steatosis, inflammation, fibrosis, and tumorigenesis, making it a potential therapeutic strategy for NAFLD-NASH and HCC.
Article
Multidisciplinary Sciences
Kanae Yumimoto, Shigeaki Sugiyama, Saori Motomura, Daisuke Takahashi, Keiichi I. Nakayama
Summary: ROS poses a risk for the transition of vertebrates from aquatic to terrestrial life, and how ancestral organisms adapted to such ROS exposure has remained a mystery. By studying the evolution of Keap1 gene, researchers found that the duplication of Keap1 gene in fish and the lower affinity of Keap1B for Cul3 contributed to robust Nrf2 induction in response to ROS exposure. Mutation of mammalian Keap1 to resemble zebrafish Keap1A resulted in an attenuated Nrf2 response and increased sensitivity to ultraviolet radiation. These findings suggest that the molecular evolution of Keap1 was essential for adaptation to terrestrial life.
Article
Multidisciplinary Sciences
Shintaro Funasaki, Atsushi Hatano, Hirokazu Nakatsumi, Daisuke Koga, Osamu Sugahara, Kanae Yumimoto, Masaya Baba, Masaki Matsumoto, Keiichi I. Nakayama
Summary: CD4(+)CD8(+) double-positive (DP) thymocytes undergo positive or negative selection based on the strength of TCR stimulation. Phosphoproteome analysis revealed that high-affinity peptide ligands induce phosphorylation of p90 ribosomal protein kinase (RSK) at Thr562. This phosphorylation triggers RSK translocation to the nucleus, where it phosphorylates the nuclear receptor Nur77, promoting its mitochondrial translocation for apoptosis induction.
Article
Biochemistry & Molecular Biology
Shigeaki Sugiyama, Kanae Yumimoto, Shun Fujinuma, Keiichi Nakayama
Summary: This study compared 10 CCR2 antagonists and found that MK0812 is the most potent inhibitor. It also demonstrated the efficacy of MK0812 in reducing lung metastasis in a mouse model.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Cell Biology
Tohru Ishitani
Summary: Morphogen gradients play a crucial role in tissue patterning. Cadherin-mediated cell competition is involved in ensuring the formation of robust morphogen gradients. This process eliminates unfit cells and corrects noisy gradients, promoting reproducible patterning.
CURRENT OPINION IN CELL BIOLOGY
(2023)