Article
Multidisciplinary Sciences
Daoxi Lei, Xiuru Zhang, Muhammad Abdul Rouf, Yoga Mahendra, Lin Wen, Yan Li, Xiaojuan Zhang, Li Li, Luming Wang, Tao Zhang, Guixue Wang, Yeqi Wang
Summary: The study revealed that par1 regulates the differentiation of lymphatic progenitors in zebrafish embryos, and its loss of function impairs lymphatic development, leading to compromised thoracic duct formation.
Article
Chemistry, Medicinal
Aoxue Wang, Junping Pei, Wen Shuai, Congcong Lin, Lu Feng, Yuxi Wang, Feng Lin, Liang Ouyang, Guan Wang
Summary: Activated Cdc42-associated kinase 1 (ACK1/TNK2) is a nonreceptor tyrosine kinase with a unique structure that can act as a transmembrane effector of receptor tyrosine kinases and play a role in epigenetic regulation. ACK1 has been shown to be a carcinogenic factor, and blocking it can inhibit cancer cell survival, proliferation, migration, and radiation resistance. Despite efforts to develop ACK1 inhibitors, no specific small molecule inhibitors have entered clinical trials yet.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Wen-Fei Wei, Hui-Ling Zhou, Pei-Yu Chen, Xiao-Lan Huang, Long Huang, Luo-Jiao Liang, Chu-Hong Guo, Chen-Fei Zhou, Lan Yu, Liang-Sheng Fan, Wei Wang
Summary: In this study, it was found that cancer-associated fibroblast (CAF)-derived PAI-1 promotes the endothelial-mesenchymal transition (EndoMT) of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). LECs undergoing EndoMT can stimulate tumor neolymphangiogenesis and promote lymphatic metastasis in CSCC. PAI-1 activates the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), leading to elevated EndoMT activity in LECs. PAI-1 could be a potential prognostic biomarker and therapeutic target for CSCC metastasis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Dongun Lee, Jeong-Hee Hong
Summary: This review summarizes the role of PyK2 in the cancer microenvironment, including its interaction with acidification and cancer-associated molecules, and highlights its relationship with cancer metastasis and potential as a therapeutic target for cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Zhenyuan Li, Tailiang Lu, Zhian Chen, Xiang Yu, Lingzhi Wang, Guodong Shen, Huilin Huang, Zhenhao Li, Yingxin Ren, Weihong Guo, Yanfeng Hu
Summary: Most early stage gastric cancer patients do not have lymph node metastases, but metastases appear in the advanced stage. However, some patients have lymph node metastases in the early stage and none in the advanced stage. To explore the molecular mechanisms involved, clinical samples were collected from patients with early and advanced stage gastric cancer with and without lymph node metastases, as well as metastatic lymph nodes. HOXA11 was identified as a key target that is upregulated in gastric cancer tissues and closely associated with lymphatic metastases. HOXA11 transcriptionally regulates TGF beta 1 expression, activates the TGF beta 1/Smad2 pathway, promotes EMT development, induces VEGF-C secretion, and lymphangiogenesis. These findings provide a plausible mechanism for HOXA11-modulated tumor lymphatic metastasis and suggest HOXA11 as a potential therapeutic target for LN-metastatic gastric cancer.
Article
Immunology
Milena Petkova, Marle Kraft, Simon Stritt, Ines Martinez-Corral, Henrik Ortsaeter, Michael Vanlandewijck, Bojana Jakic, Eulalia Baselga, Sandra D. Castillo, Mariona Graupera, Christer Betsholtz, Taija Maekinen
Summary: Researchers have identified a new subtype of lymphatic endothelial cells called iLECs, which are positive for Ptx3 and are involved in PI3K-driven lymphatic malformations. These cells recruit pro-lymphangiogenic macrophages and promote pathological lymphatic vessel growth. Understanding the specific disease pathogenesis of different vessel types could lead to the development of more efficient therapies.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jia Z. Shen, Zhixin Qiu, Qiulian Wu, Guoxin Zhang, Rebecca Harris, Dahui Sun, Juha Rantala, William D. Barshop, Linjie Zhao, Deguan Lv, Kwang-Ai Won, James Wohlschlegel, Olle Sangfelt, Heike Laman, Jeremy N. Rich, Charles Spruck
Summary: A study has identified FBXO7 as a regulator of the mesenchymal and immune evasion phenotypes of cancer cells. FBXO7 binds and stabilizes SIX1 and EYA2, promoting mesenchymal gene expression and suppressing immune-related pathways. Inhibition of EYA2 activity decreases the mesenchymal phenotype and enhances cancer cell immunogenicity, leading to improved response to immunotherapy.
Article
Chemistry, Multidisciplinary
Qiang Zhang, Sen Liu, Hongjin Wang, Kanghua Xiao, Junlin Lu, Siting Chen, Ming Huang, Ruihui Xie, Tianxin Lin, Xu Chen
Summary: The infiltration of tumor associated neutrophils (TANs) is increased and associated with poor prognosis in LN-metastatic BCa. ETV4 transcription factor enhances BCa cells-derived CXCL1/8 to recruit TANs, leading to the release of VEGFA and MMP9 from TANs, facilitating lymphangiogenesis and LN metastasis of BCa. This study reveals a novel mechanism of how tumor cells regulate TANs-induced lymphangiogenesis and LN metastasis and identifies ETV4 as a therapeutic target for LN metastasis in BCa.
Article
Biology
Nil Vanli, Jinghao Sheng, Shuping Li, Zhengping Xu, Guo-Fu Hu
Summary: RNASE4 serves as a biomarker for prostate cancer and can predict aggressiveness of the disease and enhance diagnosis accuracy. It also promotes tumor cell proliferation and angiogenesis.
COMMUNICATIONS BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Jerome W. Breslin
Summary: This review examines the challenges in treating edema and explores the physiological, cellular, and molecular mechanisms that contribute to its development. It also discusses clinical conditions associated with edema and potential future directions for research.
Article
Multidisciplinary Sciences
Hui Chen, Mindy Smith, Jasmin Herz, Tong Li, Rebecca Hasley, Cecile Le Saout, Ziang Zhu, Jie Cheng, Andres Gronda, Jose A. Martina, Pablo M. Irusta, Tatiana Karpova, Dorian B. McGavern, Marta Catalfamo
Summary: PAR1 activation in CD8 T cells accelerates calcium mobilization, facilitates granule trafficking through actin polymerization, and repositions the microtubule organizing center toward the immunological synapse. Mice lacking PAR1 exhibit reduced cytokine-producing T cells in response to viral infection, and specific deletion of PAR1 in LCMV GP33-specific CD8 T cells results in diminished expansion and effector function. These findings suggest that PAR1 plays a crucial role in T cell activation and function, offering a new therapeutic strategy to modulate CD8 T cell effector function.
Article
Multidisciplinary Sciences
Qinya Xie, Caterina Prelli Bozzo, Laura Eiben, Sabrina Noettger, Dorota Kmiec, Rayhane Nchioua, Daniela Niemeyer, Meta Volcic, Jung-Hyu Lee, Fabian Zech, Konstantin M. J. Sparrer, Christian Drosten, Frank Kirchhoff
Summary: Opposing effects of IFITMs on SARS-CoV-2 infection have been reported, but their role in other hCoVs remains unclear. This study finds that IFITM2 and/or IFITM3 are critical for efficient replication of SARS-CoV-1, SARS-CoV-2, and hCoV-OC43, but have little effect on MERS, NL63, and 229E-hCoVs. Overexpression of IFITMs inhibits all hCoVs except OC43, and impairs cell surface expression of ACE2, the entry receptor for SARS-CoVs and hCoV-NL63. These results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and demonstrate the hijacking of IFITMs by three hCoVs for efficient infection in human cells.
Article
Cell Biology
Ryoko Sato-Nishiuchi, Masamichi Doiguchi, Nanami Morooka, Kiyotoshi Sekiguchi
Summary: Polydom is an extracellular matrix protein involved in lymphatic vessel development. In this study, it was found that Polydom directly binds to Tie1, a receptor in the Angiopoietin-Tie system, and promotes lymphatic endothelial cell migration. The PI3K/Akt pathway is involved in Polydom-induced LEC migration. These findings suggest that Polydom plays a crucial role in lymphatic vessel development through Tie1 and the PI3K/Akt pathway.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Oncology
Jorge Barriuso, Raghavendar T. Nagaraju, Shreya Belgamwar, Bipasha Chakrabarty, George J. Burghel, Helene Schlecht, Lucy Foster, Elaine Kilgour, Andrew J. Wallace, Michael Braun, Caroline Dive, D. Gareth Evans, Robert G. Bristow, Mark P. Saunders, Sarah T. O'Dwyer, Omer Aziz
Summary: The study identified gene dysregulation in peritoneal metastasis that enhances tumor resistance and inflammatory changes. After adjusting for age, gender, and stage, the gene signature showed significant prognostic value for both overall survival and disease-free survival.
CLINICAL CANCER RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Gangarao Davuluri, Nicole Welch, Jinendiran Sekar, Mahesha Gangadhariah, Khaled Alsabbagh Alchirazi, Maradumane L. Mohan, Avinash Kumar, Sashi Kant, Samjhana Thapaliya, McKenzie Stine, Megan R. McMullen, Rebecca L. McCullough, George R. Stark, Laura E. Nagy, Sathyamangla V. Naga Prasad, Srinivasan Dasarathy
Summary: Despite the high clinical significance of sarcopenia in alcohol-associated cirrhosis, the mechanisms of ethanol-induced impaired protein homeostasis are poorly understood. This study identified PP2A as a key mediator in ethanol-induced dysregulation of protein balance, suggesting potential therapeutic approaches targeting the PI3K gamma-PP2A axis.
Review
Medicine, Research & Experimental
Weizhuo Lu, Zhiwu Chen, Jiyue Wen
Summary: Ischemic stroke is a common and serious disease, and neuroinflammation plays a crucial role in its progression. Microglia, astrocytes, and infiltrating immune cells are involved in the complicated neuroinflammation cascade, releasing different molecules that affect inflammation. Flavonoids, plant-specific compounds, have shown protective effects against cerebral ischemia injury by modulating the inflammatory responses.
BIOMEDICINE & PHARMACOTHERAPY
(2024)