Article
Oncology
Anxo Martinez-Ordonez, Angeles Duran, Marc Ruiz-Martinez, Tania Cid-Diaz, Xiao Zhang, Qixiu Han, Hiroto Kinoshita, Yu Muta, Juan F. Linares, Hiroaki Kasashima, Yuki Nakanishi, Mohamed Omar, Sadaaki Nishimura, Leandro Avila, Masakazu Yashiro, Kiyoshi Maeda, Tania Pannellini, Alessio Pigazzi, Giorgio Inghirami, Luigi Marchionni, Darren Sigal, Maria T. Diaz-Meco, Jorge Moscat
Summary: Mesenchymal colorectal cancer (mCRC) is characterized by accumulation of hyaluronan (HA) and reduced levels of atypical protein kinase Cs (aPKCs), which predicts poor survival. HA promotes epithelial heterogeneity and the emergence of tumor fetal metaplastic cells (TFMCs) with invasive cancer features through interactions with activated fibroblasts. In vivo HA degradation impairs mCRC tumorigenesis and enables immune checkpoint blockade therapy.
Article
Gastroenterology & Hepatology
Cambrian Y. Liu, Nandini Girish, Marie L. Gomez, Philip E. Dube, M. Kay Washington, Benjamin D. Simons, D. Brent Polk
Summary: In this study, it was found that a large squamous epithelium called squamous neo-epithelium of the colon (SNEC) exists near the anus during colitis. Squamous cells from the anus can migrate into the ulcerated colon and establish a permanent epithelium with crypt-like morphology. These squamous cells originate from a small transition zone outside the border of colonic and anal epithelium. Further research on these cells may provide new approaches for directing mucosal healing in inflammation and disease.
Article
Cell Biology
Yuanyuan Zhao, Mengmeng Guo, Fuqiang Zhao, Qian Liu, Xia Wang
Summary: In colorectal cancer (CRC), the normal tissue adjacent to the tumor undergoes molecular changes in the tumor microenvironment. Through the use of a stem cell culture system, colonic cells from different tissues were compared in terms of their clonogenicity, differentiation ability, and molecular characteristics. It was discovered that the clones from the normal adjacent tissue exhibited changes at the molecular level, with enrichment of inflammation and fibrosis-related pathways.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Thomas Sell, Christian Klotz, Matthias M. Fischer, Rosario Astaburuaga-Garcia, Susanne Krug, Jarno Drost, Hans Clevers, Christine Sers, Markus Morkel, Nils Bluethgen
Summary: Colorectal cancer progression is closely related to deregulation of intestinal differentiation trajectory. The sequential mutations of APC, KRAS, TP53, and SMAD4 enable oncogenic signaling and establish cancer hallmarks. Mass cytometry of isogenic human colon and patient-derived cancer organoids reveals a differentiation axis from normal to cancer states, shaped by the driver mutations. Cells along this axis can be influenced by subsequent mutations to promote or restrict stem cell properties. Nodes of the cancer cell signaling network remain coupled to the differentiation state. Single-cell RNA sequencing links protein signaling network to transcriptomic states with biological and clinical importance.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Xiao-Yue Chen, Kuan-Yuan Chen, Po-Hao Feng, Kang-Yun Lee, Yu-Ting Fang, You-Yin Chen, Yu-Chun Lo, Pankaj K. Bhavsar, Kian Fan Chung, Hsiao-Chi Chuang
Summary: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were found to ameliorate lung injury in acute respiratory distress syndrome (ARDS) by regulating Yes-associated protein (YAP) and promoting the differentiation of type II alveolar epithelial cells (AECII). The administration of hUC-MSCs improved pulmonary function, reduced inflammation, and mitigated lung injury in an ARDS mouse model.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Gastroenterology & Hepatology
Patrick Niekamp, Chang H. Kim
Summary: The global burden of colorectal cancer is expected to increase, and research has identified the effects of various environmental factors on its development, such as diet, the gut microbiota, and their metabolites. Microbial metabolites, including short-chain fatty acids, bile acid derivatives, indole metabolites, polyamines, trimethylamine-N-oxide, formate, and hydrogen sulfide, regulate different cell types in the intestine, leading to altered intestinal barrier, immunity, chronic inflammation, and tumorigenesis. The physical, chemical, and metabolic properties of these metabolites, along with their functions in triggering host receptors, largely determine their effects on colorectal cancer development.
Review
Oncology
Romina Judith Walter, Steffen Joachim Sonnentag, Veronique Orian-Rousseau, Leonel Munoz-Sagredo
Summary: The cancer stem cell hypothesis suggests that tumors originate from a small population of cells with self-renewal capabilities, with differentiated cells potentially having tumor-suppressive effects. Understanding cell hierarchies and plasticity is crucial for investigating the interplay between cancer stem cells and differentiated cells.
Review
Immunology
Fenyao Li, Xinxin Wang, Jin Shi, Shuting Wu, Wenbo Xing, Yan He
Summary: Dental pulp stem cells have strong immunomodulatory capabilities and can be used to treat inflammation-related diseases and autoimmune disorders. The mechanism of action is complex and may involve the regulation of immune cells through inflammatory immune-related signaling pathways.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Zhiqiang Wang, Zhou Lu, Shengli Lin, Jie Xia, Ziwen Zhong, Zhangjuan Xie, Yun Xing, Jingbo Qie, Mengxia Jiao, Yifan Li, Haoyu Wen, Pengyuan Zhao, Dan Zhang, Pinghong Zhou, Jiawen Qian, Feifei Luo, Luman Wang, Hongxiu Yu, Jie Liu, Jie Gu, Ronghua Liu, Yiwei Chu
Summary: A subset of B cells expressing leucine-tRNA-synthase-2 (LARS2) with a transforming growth factor-beta 1 (TGF-beta 1) regulatory feature has been identified in both mouse and human colorectal cancer (CRC). These cells exhibit a leucine nutrient preference and are located outside the tertiary lymphoid structure. They are associated with colorectal hyperplasia and shortened survival in CRC patients. A leucine diet can induce the generation of LARS B cells, while deletion of Lars2 gene or leucine blockage can repress CRC immunoevasion. Mechanistically, LARS2 regulates mitochondrial nicotinamide adenine dinucleotide (NAD(+)) regeneration and oxidative metabolism, involving the NAD-dependent protein deacetylase sirtuin-1 (SIRT1).
Article
Biochemistry & Molecular Biology
Behzad Shahbazi, Ladan Mafakher, Seyed Shahriar Arab, Ladan Teimoori-Toolabi
Summary: In this study, the structural basis of the Kallistatin-LRP6E1E4 complex was explored using computational methods, and the anti-proliferative, apoptotic, and cell cycle arrest activities of Kallistatin in colon cancer cell lines were evaluated. The results showed that Kallistatin had a stronger binding affinity to LRP6E3E4 compared to LRP6E1E2. The Kallistatin-LRP6E1E2 and Kallistatin-LRP6E3E4 complexes were stable during Molecular Dynamics simulation. Kallistatin exhibited higher cytotoxicity and apoptosis in the HCT116 cell line compared to the SW480 cell line, and induced cell cycle arrest at the G1 phase in both cell lines. The expression levels of B-catenin, cyclin D1, c-Myc, and LRP6 were affected by Kallistatin treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Editorial Material
Multidisciplinary Sciences
David J. J. Glass
Summary: Senescent cells in skeletal muscle promote inflammation and hinder regeneration, potentially causing harmful changes in aged muscle.
Review
Biochemistry & Molecular Biology
Ping Lyu, Yiming Song, Ruiye Bi, Zucen Li, Yali Wei, Qin Huang, Chen Cui, Dongzhe Song, Xuedong Zhou, Yi Fan
Summary: Apical periodontitis (AP) is a common inflammatory disease caused by bacterial infection in the periapical region of the tooth. The regeneration of damaged periapical alveolar bone and surrounding periodontium tissues has been a challenging task in clinical practice, but mesenchymal stem cells (MSCs) play a crucial role in mediating the immune system and promoting regeneration.
Review
Biochemistry & Molecular Biology
Asma Abdullah Nurul, Maryam Azlan, Muhammad Rajaei Ahmad Mohd Zain, Alphy Alphonsa Sebastian, Ying Zhen Fan, Mh Busra Fauzi
Summary: Osteoarthritis is characterized by cartilage degeneration and inflammation, with traditional treatment focusing on symptom relief rather than cartilage regeneration. Mesenchymal stem cells are being researched as a potential therapy for osteoarthritis due to their ability to promote cartilage repair and regeneration.
Article
Multidisciplinary Sciences
Adam E. Hall, Sebastian Other-Gee Pohl, Patrizia Cammareri, Stuart Aitken, Nicholas T. Younger, Michela Raponi, Caroline V. Billard, Alfonso Bolado Carrancio, Aslihan Bastem, Paz Freile, Fiona Haward, Ian R. Adams, Javier F. Caceres, Paula Preyzner, Alex von Kriegsheim, Malcolm G. Dunlop, Farhat V. Din, Kevin B. Myant
Summary: This study identifies dysregulated RNA splicing as a key driver of tumour cell plasticity in colorectal cancer. The splicing factor SRSF1 controls Kras splicing and maintains stemness in CRC cells, and its expression correlates with cancer stem cell markers in human tumours.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Dustin J. Flanagan, Nalle Pentinmikko, Kalle Luopajarvi, Nicky J. Willis, Kathryn Gilroy, Alexander P. Raven, Lynn Mcgarry, Johanna Englund, Anna T. Webb, Sandra Scharaw, Nadia Nasreddin, Michael C. Hodder, Rachel A. Ridgway, Emma Minnee, Nathalie Sphyris, Ella Gilchrist, Arafath K. Najumudeen, Beatrice Romagnolo, Christine Perret, Ann C. Williams, Hans Clevers, Pirjo Nummela, Marianne Lahde, Kari Alitalo, Ville Hietakangas, Ann Hedley, William Clark, Colin Nixon, Kristina Kirschner, E. Yvonne Jones, Ari Ristimaki, Simon J. Leedham, Paul Fish, Jean-Paul Vincent, Pekka Katajisto, Owen J. Sansom
Summary: The tumour suppressor APC is the most commonly mutated gene in colorectal cancer. Loss of Apc in intestinal stem cells drives the formation of adenomas in mice via increased WNT signalling, while reduced secretion of WNT ligands increases the ability of Apc-mutant intestinal stem cells to colonize a crypt. The study found that Apc-mutant cells are enriched for transcripts encoding several secreted WNT antagonists, with Notum being the most highly expressed. These cells actively inhibit the proliferation of surrounding wild-type crypt cells, outcompeting them in the niche and driving their differentiation.