Francesco Albano, Sabino Russi, Simona Laurino, Pellegrino Mazzone, Giuseppina Di Paola, Pietro Zoppoli, Elena Amendola, Chiara Balzamo, Ottavia Bartolo, Mario Ciuffi, Orazio Ignomirelli, Alessandro Sgambato, Rocco Galasso, Mario De Felice, Geppino Falco, Giovanni Calice
{"title":"Representing ECM composition and EMT pathways in gastric cancer using a new metastatic gene signature.","authors":"Francesco Albano, Sabino Russi, Simona Laurino, Pellegrino Mazzone, Giuseppina Di Paola, Pietro Zoppoli, Elena Amendola, Chiara Balzamo, Ottavia Bartolo, Mario Ciuffi, Orazio Ignomirelli, Alessandro Sgambato, Rocco Galasso, Mario De Felice, Geppino Falco, Giovanni Calice","doi":"10.3389/fcell.2024.1481818","DOIUrl":"https://doi.org/10.3389/fcell.2024.1481818","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer (GC) is an aggressive and heterogeneous malignancy marked by cellular and molecular diversity. In GC, cancer cells invade locally in the stomach at stage I and can progress to metastasis in distant organs by stage IV, where it often becomes fatal.</p><p><strong>Methods: </strong>We analyzed gene expression profiles from 719 stage I and stage IV GC patients across seven public datasets, conducting functional enrichment analysis to identify a gene signature linked to disease progression. Additionally, we developed an <i>in vitro</i> model of a simplified extracellular matrix (ECM) for cell-based assays.</p><p><strong>Results: </strong>Our analysis identified a progression-associated gene signature (<i>APOD, COL1A2, FSTL1, GEM, LUM, and SPARC</i>) that characterizes stage IV GC. This signature is associated with ECM organization and epithelial-to-mesenchymal transition (EMT), both of which influence the tumor microenvironment by promoting cell invasion and triggering EMT.</p><p><strong>Discussion: </strong>This gene signature may help identify stage I GC patients at higher risk, offering potential utility in early-stage patient management. Furthermore, our experimental ECM model may serve as a platform for investigating molecular mechanisms underlying metastatic spread in gastric cancer.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1481818"},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beiyan Tang, Wei Kang, Qiang Dong, Zhenwei Qin, Lei Duan, Xianjun Zhao, Guoqiang Yuan, Yawen Pan
{"title":"Research progress on S-palmitoylation modification mediated by the ZDHHC family in glioblastoma.","authors":"Beiyan Tang, Wei Kang, Qiang Dong, Zhenwei Qin, Lei Duan, Xianjun Zhao, Guoqiang Yuan, Yawen Pan","doi":"10.3389/fcell.2024.1413708","DOIUrl":"https://doi.org/10.3389/fcell.2024.1413708","url":null,"abstract":"<p><p>S-Palmitoylation has been widely noticed and studied in a variety of diseases. Increasing evidence suggests that S-palmitoylation modification also plays a key role in Glioblastoma (GBM). The zDHHC family, as an important member of S-palmitoyltransferases, has received extensive attention for its function and mechanism in GBM which is one of the most common primary malignant tumors of the brain and has an adverse prognosis. This review focuses on the zDHHC family, essential S-palmitoyltransferases, and their involvement in GBM. By summarizing recent studies on zDHHC molecules in GBM, we highlight their significance in regulating critical processes such as cell proliferation, invasion, and apoptosis. Specifically, members of zDHHC3, zDHHC4, zDHHC5 and others affect key processes such as signal transduction and phenotypic transformation in GBM cells through different pathways, which in turn influence tumorigenesis and progression. This review systematically outlines the mechanism of zDHHC family-mediated S-palmitoylation modification in GBM, emphasizes its importance in the development of this disease, and provides potential targets and strategies for the treatment of GBM. It also offers theoretical foundations and insights for future research and clinical applications.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1413708"},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of ABCC5 in cancer drug resistance and its potential as a therapeutic target.","authors":"Yinlong Pan, Mengmeng Wu, Huazhong Cai","doi":"10.3389/fcell.2024.1446418","DOIUrl":"https://doi.org/10.3389/fcell.2024.1446418","url":null,"abstract":"<p><p>Over 90% of treatment failures in cancer therapy can be attributed to multidrug resistance (MDR), which can develop intracellularly or through various routes. Numerous pathways contribute to treatment resistance in cancer, but one of the most significant pathways is intracellular drug efflux and reduced drug concentrations within cells, which are controlled by overexpressed drug efflux pumps. As a member of the family of ABC transporter proteins, ABCC5 (ATP Binding Cassette Subfamily C Member 5) reduces the intracellular concentration of a drug and its subsequent effectiveness using an ATP-dependent method to pump the drug out of the cell. Numerous studies have demonstrated that ABCC5 is strongly linked to both poor prognosis and poor treatment response. In addition, elevated ABCC5 expression is noted in a wide variety of malignancies. Given that ABCC5 is regulated by several pathways in a broad range of cancer types, it is a prospective target for cancer treatment. This review examined the expression, structure, function, and role of ABCC5 in various cancer types.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1446418"},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farah Mansour, Ludovica Parisi, Silvia Rihs, Isabelle Schnyder, Giorgio C La Scala, Nijas Aliu, Christos Katsaros, Martin Degen
{"title":"Immortalization of patient-derived lip cells for establishing 3D lip models.","authors":"Farah Mansour, Ludovica Parisi, Silvia Rihs, Isabelle Schnyder, Giorgio C La Scala, Nijas Aliu, Christos Katsaros, Martin Degen","doi":"10.3389/fcell.2024.1449224","DOIUrl":"10.3389/fcell.2024.1449224","url":null,"abstract":"<p><strong>Introduction: </strong>The lips fulfill various critical physiological roles besides being viewed as a fundamental aesthetic feature contributing to the perception of health and beauty. Therefore, any lip injury, abnormality, or congenital malformation, such as cleft lip, needs special attention in order to restore proper lip function and aesthetics. To achieve this goal, a better understanding of the complex lip anatomy, function, and biology is required, which can only be provided by basic research endeavors. However, the current lack of clinically relevant human lip cells and three-dimensional <i>in vitro</i> lip models, capable of replacing ethically questionable animal experimentations, represents a significant limitation in this area of research.</p><p><strong>Methods: </strong>To address these limitations, we aimed to pioneer the introduction of immortalized healthy lip- and cleft lip-derived keratinocytes. Primary keratinocytes were isolated from patients' samples and immortalized by introducing the catalytic domain of telomerase, combined with the targeted knockdown of the cell cycle inhibitor gene, <i>p16</i> <sup><i>INK4A</i></sup> . We then focused on validating the newly established cell lines by comparing their genetic stability and key phenotypic features with their primary keratinocyte counterparts.</p><p><strong>Results: </strong>The newly established immortalized keratinocyte cell lines demonstrated genetic stability and preserved the main phenotypic characteristics of primary keratinocytes, such as cellular morphology and differentiation capacity. Three-dimensional lip models, generated using these cell lines, proved to be effective and convenient platforms for screening applications, including wound healing and microbial infection of the lip epithelium.</p><p><strong>Discussion: </strong>The establishment of immortalized keratinocytes derived from healthy and cleft lips represents a significant achievement in lip research. These cell lines and the associated three-dimensional lip models are valuable tools that can be used as convenient screening platforms for various assays in a multitude of lip-related research areas, including dermatology, skin care, wound healing, tissue engineering, and craniofacial anomalies. This work opens new avenues in studying lip abnormalities and provides unique tools for personalized medicine approaches beneficial to patients.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1449224"},"PeriodicalIF":4.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengxin Li, Xuanzhong Wang, Jinghui Hong, Juanjuan Mao, Jiasi Chen, Xuyang Chen, Ye Du, Dong Song
{"title":"Transglutaminase 2 in breast cancer metastasis and drug resistance.","authors":"Mengxin Li, Xuanzhong Wang, Jinghui Hong, Juanjuan Mao, Jiasi Chen, Xuyang Chen, Ye Du, Dong Song","doi":"10.3389/fcell.2024.1485258","DOIUrl":"10.3389/fcell.2024.1485258","url":null,"abstract":"<p><p>Transglutaminase 2 (TG2) is a widely distributed multifunctional protein with various enzymatic and non-enzymatic activities. It is becoming increasingly evident that high levels of TG2 in tumors induce the occurrence of epithelial to mesenchymal transition (EMT) and the acquisition of stem cell-like phenotypes, promoting tumor metastasis and drug resistance. By regulating intracellular and extracellular signaling pathways, TG2 promotes breast cancer metastasis to lung, brain, liver and bone, as well as resistance to various chemotherapy drugs including docetaxel, doxorubicin, platinum and neratinib. More importantly, recent studies described the involvement of TG2 in PD-1/PD-L1 inhibitors resistance. An in-depth understanding of the role that TG2 plays in the progression of metastasis and drug resistance will offer new therapeutic targets for breast cancer treatment. This review covers the extensive and rapidly growing field of the role of TG2 in breast cancer. Based on the role of TG2 in EMT, we summarize TG2-related signaling pathways in breast cancer metastasis and drug resistance and discuss TG2 as a therapeutic target.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1485258"},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Using different zebrafish models to explore liver regeneration.","authors":"Dashuang Mo, Mengzhu Lv, Xiaoyu Mao","doi":"10.3389/fcell.2024.1485773","DOIUrl":"10.3389/fcell.2024.1485773","url":null,"abstract":"<p><p>The liver possesses an impressive capability to regenerate following various injuries. Given its profound implications for the treatment of liver diseases, which afflict millions globally, liver regeneration stands as a pivotal area of digestive organ research. Zebrafish (<i>Danio rerio</i>) has emerged as an ideal model organism in regenerative medicine, attributed to their remarkable ability to regenerate tissues and organs, including the liver. Many fantastic studies have been performed to explore the process of liver regeneration using zebrafish, especially the extreme hepatocyte injury model. Biliary-mediated liver regeneration was first discovered in the zebrafish model and then validated in mammalian models and human patients. Considering the notable expansion of biliary epithelial cells in many end-stage liver diseases, the promotion of biliary-mediated liver regeneration might be another way to treat these refractory liver diseases. To date, a comprehensive review discussing the current advancements in zebrafish liver regeneration models is lacking. Therefore, this review aims to investigate the utility of different zebrafish models in exploring liver regeneration, highlighting the genetic and cellular insights gained and discussing the potential translational impact on human health.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1485773"},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kurt T K Giuliani, Benjamin C Adams, Helen G Healy, Andrew J Kassianos
{"title":"Regulated cell death in chronic kidney disease: current evidence and future clinical perspectives.","authors":"Kurt T K Giuliani, Benjamin C Adams, Helen G Healy, Andrew J Kassianos","doi":"10.3389/fcell.2024.1497460","DOIUrl":"10.3389/fcell.2024.1497460","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is the progressive loss of kidney function/structure over a period of at least 3 months. It is characterised histologically by the triad of cell loss, inflammation and fibrosis. This literature review focuses on the forms of cell death that trigger downstream inflammation and fibrosis, collectively called regulated cell death (RCD) pathways. Discrete forms of RCD have emerged as central mediators of CKD pathology. In particular, pathways of regulated necrosis - including mitochondrial permeability transition pore (mPTP)-mediated necrosis, necroptosis, ferroptosis and pyroptosis - have been shown to mediate kidney pathology directly or through the release of danger signals that trigger a pro-inflammatory response, further amplifying tissue injury in a cellular process called necroinflammation. Despite accumulating evidence in pre-clinical models, no clinical studies have yet targeted these RCD modes in human CKD. The review summarizes recent advances in our understanding of RCD pathways in CKD, looks at inter-relations between the pathways (with the emphasis on propagation of death signals) and the evidence for therapeutic targeting of molecules in the RCD pathways to prevent or treat CKD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1497460"},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huanxiao Shi, Yi Ding, Pingxin Sun, Zhuman Lv, Chunyan Wang, Haoxin Ma, Junyu Lu, Bing Yu, Wenlin Li, Chao Wang
{"title":"Chemical approaches targeting the hurdles of hepatocyte transplantation: mechanisms, applications, and advances.","authors":"Huanxiao Shi, Yi Ding, Pingxin Sun, Zhuman Lv, Chunyan Wang, Haoxin Ma, Junyu Lu, Bing Yu, Wenlin Li, Chao Wang","doi":"10.3389/fcell.2024.1480226","DOIUrl":"10.3389/fcell.2024.1480226","url":null,"abstract":"<p><p>Hepatocyte transplantation (HTx) has been a novel cell-based therapy for severe liver diseases, as the donor livers for orthotopic liver transplantation are of great shortage. However, HTx has been confronted with two main hurdles: limited high-quality hepatocyte sources and low cell engraftment and repopulation rate. To cope with, researchers have investigated on various strategies, including small molecule drugs with unique advantages. Small molecules are promising chemical tools to modulate cell fate and function for generating high quality hepatocyte sources. In addition, endothelial barrier, immune responses, and low proliferative efficiency of donor hepatocytes mainly contributes to low cell engraftment and repopulation rate. Interfering these biological processes with small molecules is beneficial for improving cell engraftment and repopulation. In this review, we will discuss the applications and advances of small molecules in modulating cell differentiation and reprogramming for hepatocyte resources and in improving cell engraftment and repopulation as well as its underlying mechanisms.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1480226"},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Implications of DNA damage in chronic lung disease.","authors":"Dingning Zhang, Tong Sun, Jiahui Bao, Jianhua Fu","doi":"10.3389/fcell.2024.1436767","DOIUrl":"10.3389/fcell.2024.1436767","url":null,"abstract":"<p><p>DNA plays an indispensable role in ensuring the perpetuation of life and safeguarding the genetic stability of living organisms. The emergence of diseases linked to a wide spectrum of responses to DNA damage has garnered increasing attention within the scientific community. There is growing evidence that patterns of DNA damage response in the lungs are associated with the onset, progression, and treatment of chronic lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and bronchopulmonary dysplasia (BPD). Currently, some studies have analyzed the mechanisms by which environmental factors induce lung DNA damage. In this article, we summarize inducible factors of lung DNA damage, current indicators, and methods for diagnosing DNA damage in chronic lung diseases and explore repair mechanisms after DNA damage including nonhomologous end-joining and homology-directed repair end joining pathways. Additionally, drug treatments that may reduce DNA damage or promote repair after it occurs in the lungs are briefly described. In general, more accurate assessment of the degree of lung DNA damage caused by various factors is needed to further elucidate the mechanism of lung DNA damage and repair after damage, so as to search for potential therapeutic targets.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1436767"},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ksenia Yrigoin, Kaitlyn N Bernard, Maria A Castaño, Ondine Cleaver, Saulius Sumanas, George E Davis
{"title":"Enhancing human capillary tube network assembly and maturation through upregulated expression of pericyte-derived TIMP-3.","authors":"Ksenia Yrigoin, Kaitlyn N Bernard, Maria A Castaño, Ondine Cleaver, Saulius Sumanas, George E Davis","doi":"10.3389/fcell.2024.1465806","DOIUrl":"10.3389/fcell.2024.1465806","url":null,"abstract":"<p><p>In this study, we identify and characterize new molecular determinants that optimize human capillary tube network assembly. Our lab has previously reported a novel, serum free-defined 3D co-culture model using human endothelial cells (ECs) and human pericytes whereby EC-lined tubes form and co-assemble with pericytes, but when these cultures are maintained at or beyond 5 days, tubes become progressively wider and unstable. To address this issue, we generated novel human pericytes that carry a tissue inhibitor of metalloproteinase (TIMP)-3 transgene which can be upregulated following doxycycline addition. EC-pericyte co-cultures established in the presence of doxycycline demonstrated marked enhancement of capillary network assembly including dramatic narrowing of capillary tube widths to an average of 8 µm (physiologic capillary tube width), increased tube lengths, increased tube branching, and robust stimulation of basement membrane matrix assembly, particularly with collagen type IV and fibronectin deposition compared to controls. These substantial changes depend not only on induction of pericyte TIMP-3, but also on recruitment of pericytes to EC tubes. Blockade of pericyte recruitment prevents these dramatic capillary network alterations suggesting that EC-pericyte interactions and induction of pericyte TIMP-3 are necessary together to coordinate and facilitate capillary assembly and maturation. Overall, this work is critical for our basic understanding of capillary formation, but also for the ability to reproducibly generate stabilized networks of capillary tubes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1465806"},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}