Review
Biochemistry & Molecular Biology
Maria Cristina Rapanotti, Elisa Cugini, Marzia Nuccetelli, Alessandro Terrinoni, Cosimo Di Raimondo, Paolo Lombardo, Gaetana Costanza, Terenzio Cosio, Piero Rossi, Augusto Orlandi, Elena Campione, Sergio Bernardini, Marcel Blot-Chabaud, Luca Bianchi
Summary: Studies have shown that MCAM/MUC18/CD146 plays a crucial role in the progression of malignant melanoma, serving as a potential target and acting during the disease spreading progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Weichao Zhang, Xi Yang, Yingxiang Li, Linchen Yu, Bokai Zhang, Jianchao Zhang, Woo Jung Cho, Varsha Venkatarangan, Liang Chen, Bala Bharathi Burugula, Sarah Bui, Yanzhuang Wang, Cunming Duan, Jacob O. Kitzman, Ming Li
Summary: In this study, researchers identify TMEM251 as the first regulator of the M6P modification, which is necessary for correct lysosomal targeting. Deletion of TMEM251 results in mistargeting of lysosomal enzymes and accumulation of undigested materials. These findings provide insights into a newly discovered human disease caused by TMEM251 mutations.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Kohei Kawasaki, Atsushi Kasamatsu, Toshiaki Ando, Tomoaki Saito, Takafumi Nobuchi, Ryunosuke Nozaki, Manabu Iyoda, Katsuhiro Uzawa
Summary: PAFR is a therapeutic target for modulating CDDP sensitivity in oral squamous cell carcinoma (OSCC) cells. The specific inhibitor of PAFR, ginkgolide B (GB), can enhance chemosensitivity to CDDP and promote apoptosis. GB may serve as a novel drug to enhance combination chemotherapy with CDDP for OSCC patients.
Article
Biochemistry & Molecular Biology
Xia Zou, Jishun Lu, Yao Deng, Qiannan Liu, Xialin Yan, Yalu Cui, Xiao Xiao, Meng Fang, Fang Yang, Hiromichi Sawaki, Takashi Sato, Binbin Tan, Xiaoyan Lu, Bo Feng, Atsushi Kuno, Hisashi Narimatsu, Chunfang Gao, Yan Zhang
Summary: This study revealed that ST6GAL1 and alpha 2,6 sialylation are negatively correlated with HCC cell metastasis. ST6GAL1 overexpression inhibits HCC cell migration and invasion in vitro and suppresses HCC metastasis in vivo, possibly through regulating MCAM expression.
Article
Medicine, General & Internal
Jordi Roca-Ferrer, Maria Perez-Gonzalez, Isam Alobid, Valeria Tubita, Mireya Fuentes, Marina Bantula, Rosa Munoz-Cano, Antonio Valero, Inaki Izquierdo, Joaquim Mullol, Jacopo Galli
Summary: This study aimed to assess the role of the Platelet-Activating Factor (PAF)/receptor (PAFR) system in chronic rhinosinusitis with nasal polyps (CRSwNP). The study found that PAFR protein was expressed in nasal mucosa and nasal polyps, and Lyso-PAF concentrations were higher in nasal polyps of asthmatic patients. These findings suggest that the PAF/PAFR system may play a role in CRSwNP pathogenesis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Stephanie A. Renna, Steven E. McKenzie, James V. Michael
Summary: Protease-activated receptors (PARs) are membrane proteins cleaved by proteases, such as thrombin, which activate them by revealing a tethered ligand. PARs play critical roles in platelet function and are potential targets for anti-platelet therapies. While genetically modified mouse models have provided insights into platelet PAR physiology, there are limitations. This review summarizes the differences in PAR expression and function between mice and humans, and highlights new tools for studying human physiology in mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Hyungsoo Kim, Yongmei Feng, Rabi Murad, Joanna Pozniak, Carl Pelz, Yeqing Chen, Bhavik Dalal, Rosalie Sears, Eduard Sergienko, Michael Jackson, Eytan Ruppin, Meenhard Herlyn, Curtis Harris, Jean-Christophe Marine, Victoria Klepsch, Gottfried Baier, Ze'ev A. Ronai
Summary: The orphan nuclear receptor NR2F6 has a tumor-intrinsic function in regulating antitumor immunity. It plays a role in tumor development and the abundance of CD8(+) T cells. Blocking NR2F6 enhances the efficacy of PD-1 therapy and could be a promising anticancer treatment strategy.
Letter
Oncology
Hengyu Li, Pinghua Yang, JingHan Wang, Jin Zhang, Qianyun Ma, Yingjie Jiang, Yani Wu, Tao Han, Daimin Xiang
Summary: Tumor-associated macrophages (TAMs) promote the activation of hepatic leukemia factor (HLF) in triple-negative breast cancer (TNBC) cells through the secretion of transforming growth factor-beta1 (TGF-beta 1) and subsequently, HLF transactivates gamma-glutamyltransferase 1 (GGT1) to enhance ferroptosis resistance. This process drives TNBC cell proliferation, metastasis, and cisplatin resistance. Additionally, TNBC cells activate the JAK2/STAT3 axis to induce TGF-beta 1 secretion by TAMs, forming a feed-forward circuit. The combination of HLF and GGT1 values can improve the accuracy of TNBC patient prognosis.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Daisuke Mizutani, Haruhiko Tokuda, Takashi Onuma, Kodai Uematsu, Daiki Nakashima, Kyohei Ueda, Tomoaki Doi, Yukiko Enomoto, Rie Matsushima-Nishiwaki, Shinji Ogura, Hiroki Iida, Osamu Kozawa, Toru Iwama
Summary: Amyloid beta protein negatively regulates human platelet activation, which may contribute to intracerebral hemorrhage.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Noriaki Kamio, Mayumi Hayata, Muneaki Tamura, Hajime Tanaka, Kenichi Imai
Summary: Chronic periodontitis is a risk factor for pneumonia, and periodontopathic bacteria enhance pneumococcal adhesion to human alveoli by inducing PAFR expression. Among the virulence factors of Porphyromonas gingivalis, gingipains play a key role in this process.
Review
Cell Biology
Carl G. Gahmberg, Mikaela Gronholm, Sudarrshan Madhavan
Summary: Most cells express multiple integrins, which can respond to cellular functions and needs through their activation state and regulation of each other. The mechanisms of integrin crosstalk are not fully understood, but they likely involve intracellular signaling pathways shared with other cell surface receptors. Phosphorylation of integrins and key intracellular molecules play a pivotal role in integrin-cytoplasmic interactions and affect integrin activity and crosstalk. Integrin beta-chains are central in regulating crosstalk. Additionally, crosstalk may also occur between integrins and related receptors such as adhesion receptors, growth factor, and SARS-CoV-2 receptors.
Review
Nutrition & Dietetics
Rajendran Harishkumar, Sakshi Hans, Janelle E. Stanton, Andreas M. Grabrucker, Ronan Lordan, Ioannis Zabetakis
Summary: This review discusses the role of platelet-activating factor (PAF) and its receptor in inflammatory diseases and atherosclerotic cardiovascular diseases, with a focus on how inhibiting PAF-R can reduce cardiovascular disease risk. Research suggests that dietary factors may modulate PAF metabolism and PAF-R function to regulate disease development.
Article
Pharmacology & Pharmacy
Maria Amparo Blanch-Ruiz, Ainhoa Sanchez-Lopez, Cesar Rios-Navarro, Raquel Ortega-Luna, Victor Collado-Diaz, Samuel Orden, Maria Angeles Martinez-Cuesta, Juan V. Esplugues, Angeles Alvarez
Summary: This study investigates the role of neutrophils in abacavir-induced thrombosis. It reveals that abacavir activates neutrophils, leading to interactions between platelets and neutrophils, which in turn promotes thrombosis.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Hematology
Tanvi Rudran, Silvio Antoniak, Matthew J. Flick, Mark H. Ginsberg, Alisa S. Wolberg, Wolfgang Bergmeier, Robert H. Lee
Summary: This study investigated the specific receptors and signaling pathways required for platelet function in thromboelastography (TEG) using genetic and pharmacologic inhibition of platelet proteins in mouse and human blood samples. The results showed that standard TEG is not sensitive to platelet signaling pathways critical for integrin inside-out activation and platelet hemostatic function. Furthermore, this study provides the first evidence that PARs and glycoprotein VI play redundant roles in platelet-mediated clot contraction in TEG.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Hao Li, Wang Jiang, Shi-Rong Zhang, Peng-Cheng Li, Tian-Jiao Li, Wei Jin, Hua-Xiang Xu, Xian-Jun Yu, Liang Liu
Summary: This study found that CD41+/CD62P+ platelets are closely associated with the prognosis of pancreatic ductal adenocarcinoma (PDAC). High levels of CD41+/CD62P+ platelets were correlated with microvascular invasion, advanced AJCC stage, and high CA19-9 level, and independently predicted a poor prognosis for resectable PDAC. Mechanistically, Panx1 in CD41+/CD62P+ platelets promotes PDAC cell invasion and metastasis by enhancing IL-1 beta secretion through the phosphorylation of p38 MAPK. In addition, a novel compound named PC63435 was synthesized, which blocked the Panx1/IL-1 beta pathway and reduced the proportion of CD41+/CD62P+ platelets, leading to the suppression of PDAC tumor invasion and metastasis.
Article
Biochemistry & Molecular Biology
Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung
Summary: This study reports the development of two novel Gal-9-neutralizing antibodies that effectively protect human T cells from Gal-9-induced cell death and promote T cell-mediated killing of tumor cells. These findings demonstrate the potential of targeting Gal-9 for cancer immunotherapy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jian Tu, Zijun Huo, Yao Yu, Dandan Zhu, An Xu, Mo-Fan Huang, Ruifeng Hu, Ruoyu Wang, Julian A. Gingold, Yi-Hung Chen, Kuang-Lei Tsai, Nicolas R. Forcioli-Conti, Sarah X. L. Huang, Thomas R. Webb, Jie Su, Danielle A. Bazer, Peilin Jia, Jason T. Yustein, Lisa L. Wang, Mien-Chie Hung, Zhongming Zhao, Chad D. Huff, Jingnan Shen, Ruiying Zhao, Dung-Fang Lee
Summary: The study reveals that the spliceosome is an up-regulated target in RB1-mutant cells responding to oncogenic stress, and pRB and E2F3a coregulate spliceosomal gene expression, affecting cell proliferation and tumorigenesis. These findings suggest that the spliceosomal machinery could be a potential therapeutic vulnerability for pRB-deficient cancers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yun-Long Wang, Wan-Wen Zhao, Shao-Mei Bai, Li-Li Feng, Shu-Ying Bie, Li Gong, Fang Wang, Ming-Biao Wei, Wei-Xing Feng, Xiao-Lin Pang, Cao-Litao Qin, Xin-Ke Yin, Ying-Nai Wang, Weihua Zhou, Daniel R. Wahl, Quentin Liu, Ming Chen, Mien-Chie Hung, Xiang-Bo Wan
Summary: MRNIP forms liquid-like condensates to promote DSB repair. It concentrates the MRN complex to the damaged DNA in the nucleus, accelerating DSB sensing and end resection.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Wei-Jan Wang, Yeh Chen, Wen-Chi Su, Yen-Yi Liu, Wan-Jou Shen, Wei-Chao Chang, Sheng-Teng Huang, Cheng-Wen Lin, Yu-Chuan Wang, Chia-Shin Yang, Mei-Hui Hou, Yu-Chi Chou, Yang-Chang Wu, Shao-Chun Wang, Mien-Chie Hung
Summary: In this study, we identified a naturally derived compound called peimine, extracted from Fritillaria, that can inhibit viral infection of SARS-CoV-2 variants of concern (VOCs) in lung cells. Peimine blocks viral entry by interfering with the interaction between the spike protein and ACE2. Molecular docking analysis showed that peimine has a strong binding affinity for the N501Y mutation in the spike protein. Furthermore, Fritillaria was found to significantly inhibit SARS-CoV-2 viral infection. These findings suggest that peimine and Fritillaria could be potential drugs and food sources for COVID-19 patients.
JOURNAL OF FOOD BIOCHEMISTRY
(2022)
Article
Cell Biology
Yun-Long Wang, Wan-Wen Zhao, Shao-Mei Bai, Yan Ma, Xin-Ke Yin, Li-Li Feng, Guang-Dong Zeng, Fang Wang, Wei-Xing Feng, Jian Zheng, Ying-Nai Wang, Bing Zeng, Quentin Liu, Mien-Chie Hung, Xiang-Bo Wan
Summary: The research revealed the crucial role of radiation-induced paraspeckles in DNA repair and tumor radioresistance, offering a new insight into the ribosome-independent function of ribosomal proteins.
CELL DEATH & DISEASE
(2022)
Article
Immunology
Rodney Cheng-En Hsieh, Sunil Krishnan, Ren-Chin Wu, Akash R. Boda, Arthur Liu, Michelle Winkler, Wen-Hao Hsu, Steven Hsesheng Lin, Mien-Chie Hung, Li-Chuan Chan, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Ricardo Alexandre De Azevedo, Yung-Chih Chou, Ronald A. DePinho, Matthew Gubin, Eduardo Vilar, Chao Hsien Chen, Ravaen Slay, Priyamvada Jayaprakash, Shweta Mahendra Hegde, Genevieve Hartley, Spencer T. Lea, Rishika Prasad, Brittany Morrow, Coline Agnes Couillault, Madeline Steiner, Chun-Chieh Wang, Bhanu Prasad Venkatesulu, Cullen Taniguchi, Yon Son Betty Kim, Junjie Chen, Nils-Petter Rudqvist, Michael A. Curran
Summary: Radiation therapy induces up-regulation of CD47 and PD-L1 through the ATR-mediated DNA repair signaling pathway in CRC cells, which limits TAA cross-presentation and immune activation. Combination therapy with anti-SIRP alpha and anti-PD-1 reverses immune resistance, promotes TAA cross-presentation and robust antitumor immune priming.
SCIENCE IMMUNOLOGY
(2022)
Article
Oncology
Yu-Yi Chu, Mei-Kuang Chen, Yongkun Wei, Heng-Huan Lee, Weiya Xia, Ying-Nai Wang, Clinton Yam, Jennifer L. Hsu, Hung-Ling Wang, Wei-Chao Chang, Hirohito Yamaguchi, Zhou Jiang, Chunxiao Liu, Ching-Fei Li, Lei Nie, Li-Chuan Chan, Yuan Gao, Shao-Chun Wang, Jinsong Liu, Shannon N. Westin, Sanghoon Lee, Anil K. Sood, Liuqing Yang, Gabriel N. Hortobagyi, Dihua Yu, Mien-Chie Hung
Summary: This study reveals that anaplastic lymphoma kinase (ALK) phosphorylates CDK9 at tyrosine-19, leading to homologous recombination repair and resistance to PARP inhibitors. Combining ALK and PARP inhibitors shows promising results in reducing tumor growth and improving survival. The expression of phosphorylated ALK is associated with resistance to PARP inhibitors.
Article
Oncology
Yi-Chuan Li, Hirohito Yamaguchi, Yen-Yi Liu, Kai-Cheng Hsu, Ting-Hsuan Sun, Pei-Chi Sun, Mien-Chie Hung
Summary: This article investigates the interaction between ribonuclease 1 (RNase1) and EphA4 and reveals their structure and role in cellular activation. The study suggests that electrostatic force plays a crucial role in the binding and activation of RNase1 and EphA4.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Chun-Te Ho, Shih-Pei Lin, Ling-Ming Tseng, Mien-Chie Hung, Shih-Chieh Hung
Summary: This study found that a mutant form of Snail reduced the expression of Src in luminal A breast cancer cells and enhanced their migration and invasion abilities, while reducing their capacity to form tumor spheres. Additionally, human luminal A breast cancer samples showed a negative correlation between Vimentin and Src expression.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Chen-Shiou Wu, Hsiu-Mei Chiang, Yeh Chen, Chung-Yu Chen, Hsiao-Fan Chen, Wen-Chi Su, Wei-Jan Wang, Yu-Chi Chou, Wei-Chao Chang, Shao-Chun Wang, Mien-Chie Hung
Summary: This research explores natural plant extracts that have the potential to combat SARS-CoV-2 and provide alternative options for prevention and disinfection. The study identifies coffee leaf extract as an effective inhibitor of SARS-CoV-2 infection in various strains. Additionally, the extract proves to be more potent at preventing viral entry into cells when applied topically than the standard disinfectant ethanol. Compounds such as caffeine, chlorogenic acid, quinic acid, and mangiferin are found to be associated with the extract's antiviral activity.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Immunology
Poyee Lau, Guanxiong Zhang, Shuang Zhao, Long Liang, Hailun Zhang, Guowei Zhou, Mien-Chie Hung, Xiang Chen, Hong Liu
Summary: This study reveals the important role of SPHK1 in tumor immunity and shows that its inhibition can suppress tumor growth and promote antitumor immunity. Additionally, SPHK1 and MTA3 are identified as biological markers for predicting the efficacy of anti-PD-1 mAb therapy in melanoma patients.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Oncology
Zhen Xue, Shuang Zheng, Dongli Linghu, Boning Liu, Yi Yang, Mei-Kuang Chen, Hua Huang, Jiaming Song, Hongyue Li, Jing Wang, Mien-Chie Hung, Diansheng Zhong, Linlin Sun
Summary: PD-L1 plays a crucial role in DNA damage repair in cancer cells and can enhance the efficacy of existing immunotherapy by modulating pathways related to innate immunity.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Fu Ou-Yang, Chung-Liang Li, Chia-Chi Chen, Yi-Chun Shen, Sin-Hua Moi, Chi-Wen Luo, Wei-Ya Xia, Ying-Nai Wang, Heng-Huan Lee, Lu-Hai Wang, Shao-Chun Wang, Mei-Ren Pan, Ming-Feng Hou, Mien-Chie Hung
Summary: This study found that de-glycosylation of tumor cell surface PD-L1 staining is significantly correlated with clinical response in atezolizumab treatment for breast cancer. These findings suggest that de-glycosylation procedure may serve as a patient stratification strategy and should be further explored.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
David J. H. Shih, Mei-Kuang Chen, Jun Yin, Daniel J. McGrail, Hui Dai, Rongbin Wei, Jing Zhang, Wenjin Jim Zheng, Kim-Anh Do, Liuqing Yang, Mien-Chie Hung, Shiaw-Yih Lin
Summary: This study developed a bioinformatic strategy for identifying candidate drugs to overcome acquired resistance in cancer treatment. By analyzing transcriptomic data and compound perturbation profiles, the authors discovered a transcriptional adaptation deficiency in resistant clones of breast cancer cells treated with PARP inhibitors. They successfully validated the vulnerability induced by this deficiency and suggested a new strategy for precision oncology.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Medical Informatics
Lili Feng, Zhenyu Liu, Chaofeng Li, Zhenhui Li, Xiaoying Lou, Lizhi Shao, Yunlong Wang, Yan Huang, Haiyang Chen, Xiaolin Pang, Shuai Liu, Fang He, Jian Zheng, Xiaochun Meng, Peiyi Xie, Guanyu Yang, Yi Ding, Mingbiao Wei, Jingping Yun, Mien-Chie Hung, Weihua Zhou, Dantel R. Wahl, Ping Lan, Jie Tian, Xiangbo Wan
Summary: Accurate prediction of pathological complete response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer was achieved using an artificial intelligence radiopathomics integrated model based on pretreatment MRI and H&E-stained biopsy slides. The model, RAPIDS, showed high accuracy and outperformed single-modality prediction models, providing a novel tool for individualized management of locally advanced rectal cancer.
LANCET DIGITAL HEALTH
(2022)