Seminars in cancer biology最新文献

{"title":"RNA regulatory mechanisms controlling TGF-β signaling and EMT in cancer","authors":"Cameron P. Bracken ,&nbsp;Gregory J. Goodall ,&nbsp;Philip A. Gregory","doi":"10.1016/j.semcancer.2024.06.001","DOIUrl":"10.1016/j.semcancer.2024.06.001","url":null,"abstract":"<div><p>Epithelial-mesenchymal transition (EMT) is a major contributor to metastatic progression and is prominently regulated by TGF-β signalling. Both EMT and TGF-β pathway components are tightly controlled by non-coding RNAs - including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) - that collectively have major impacts on gene expression and resulting cellular states. While miRNAs are the best characterised regulators of EMT and TGF-β signaling and the miR-200-ZEB1/2 feedback loop plays a central role, important functions for lncRNAs and circRNAs are also now emerging. This review will summarise our current understanding of the roles of non-coding RNAs in EMT and TGF-β signaling with a focus on their functions in cancer progression.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"102 ","pages":"Pages 4-16"},"PeriodicalIF":12.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X24000439/pdfft?md5=d6b7a1b203085fb93f06e9ca6c92ff35&pid=1-s2.0-S1044579X24000439-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gene for all seasons: The evolutionary consequences of HIF-1 in carcinogenesis, tumor growth and metastasis","authors":"Ranjini Bhattacharya ,&nbsp;Joel S. Brown ,&nbsp;Robert A. Gatenby ,&nbsp;Arig Ibrahim-Hashim","doi":"10.1016/j.semcancer.2024.06.003","DOIUrl":"10.1016/j.semcancer.2024.06.003","url":null,"abstract":"<div><p>Oxygen played a pivotal role in the evolution of multicellularity during the Cambrian Explosion. Not surprisingly, responses to fluctuating oxygen concentrations are integral to the evolution of cancer—a disease characterized by the breakdown of multicellularity. Poorly organized tumor vasculature results in chaotic patterns of blood flow characterized by large spatial and temporal variations in intra-tumoral oxygen concentrations. Hypoxia-inducible growth factor (HIF-1) plays a pivotal role in enabling cells to adapt, metabolize, and proliferate in low oxygen conditions. HIF-1 is often constitutively activated in cancers, underscoring its importance in cancer progression. Here, we argue that the phenotypic changes mediated by HIF-1, in addition to adapting the cancer cells to their local environment, also “pre-adapt” them for proliferation at distant, metastatic sites. HIF-1-mediated adaptations include a metabolic shift towards anaerobic respiration or glycolysis, activation of cell survival mechanisms like phenotypic plasticity and epigenetic reprogramming, and formation of tumor vasculature through angiogenesis. Hypoxia induced epigenetic reprogramming can trigger epithelial to mesenchymal transition in cancer cells—the first step in the metastatic cascade. Highly glycolytic cells facilitate local invasion by acidifying the tumor microenvironment. New blood vessels, formed due to angiogenesis, provide cancer cells a conduit to the circulatory system. Moreover, survival mechanisms acquired by cancer cells in the primary site allow them to remodel tissue at the metastatic site generating tumor promoting microenvironment. Thus, hypoxia in the primary tumor promoted adaptations conducive to all stages of the metastatic cascade from the initial escape entry into a blood vessel, intravascular survival, extravasation into distant tissues, and establishment of secondary tumors.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"102 ","pages":"Pages 17-24"},"PeriodicalIF":12.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X24000452/pdfft?md5=7cc6690e16b91210d964ab28430a4b0f&pid=1-s2.0-S1044579X24000452-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles in glioblastoma: Biomarkers and therapeutic tools.","authors":"Ilaria Cela, Emily Capone, Gianluca Trevisi, Gianluca Sala","doi":"10.1016/j.semcancer.2024.04.003","DOIUrl":"10.1016/j.semcancer.2024.04.003","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive tumor among the gliomas and intracranial tumors and to date prognosis for GBM patients remains poor, with a median survival typically measured in months to a few years depending on various factors. Although standardized therapies are routinely employed, it is clear that these strategies are unable to cope with heterogeneity and invasiveness of GBM. Furthermore, diagnosis and monitoring of responses to therapies are directly dependent on tissue biopsies or magnetic resonance imaging (MRI) techniques. From this point of view, liquid biopsies are arising as key sources of a variety of biomarkers with the advantage of being easily accessible and monitorable. In this context, extracellular vesicles (EVs), physiologically shed into body fluids by virtually all cells, are gaining increasing interest both as natural carriers of biomarkers and as specific signatures even for GBM. What makes these vesicles particularly attractive is they are also emerging as therapeutical vehicles to treat GBM given their native ability to cross the blood-brain barrier (BBB). Here, we reviewed recent advances on the use of EVs as biomarker for liquid biopsy and nanocarriers for targeted delivery of anticancer drugs in glioblastoma.</p>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":" ","pages":"25-43"},"PeriodicalIF":14.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting senescent cells to reshape the tumor microenvironment and improve anticancer efficacy","authors":"Birong Jiang ,&nbsp;Wei Zhang ,&nbsp;Xuguang Zhang ,&nbsp;Yu Sun","doi":"10.1016/j.semcancer.2024.05.002","DOIUrl":"https://doi.org/10.1016/j.semcancer.2024.05.002","url":null,"abstract":"<div><p>Cancer is daunting pathology with remarkable breadth and scope, spanning genetics, epigenetics, proteomics, metalobomics and cell biology. Cellular senescence represents a stress-induced and essentially irreversible cell fate associated with aging and various age-related diseases, including malignancies. Senescent cells are characterized of morphologic alterations and metabolic reprogramming, and develop a highly active secretome termed as the senescence-associated secretory phenotype (SASP). Since the first discovery, senescence has been understood as an important barrier to tumor progression, as its induction in pre-neoplastic cells limits carcinogenesis. Paradoxically, senescent cells arising in the tumor microenvironment (TME) contribute to tumor progression, including augmented therapeutic resistance. In this article, we define typical forms of senescent cells commonly observed within the TME and how senescent cells functionally remodel their surrounding niche, affect immune responses and promote cancer evolution. Furthermore, we highlight the recently emerging pipelines of senotherapies particularly senolytics, which can selectively deplete senescent cells from affected organs <em>in vivo</em> and impede tumor progression by restoring therapeutic responses and securing anticancer efficacies. Together, co-targeting cancer cells and their normal but senescent counterparts in the TME holds the potential to achieve increased therapeutic benefits and restrained disease relapse in future clinical oncology.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"101 ","pages":"Pages 58-73"},"PeriodicalIF":14.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X24000361/pdfft?md5=021560fd6bcbef775d840491f4108ba6&pid=1-s2.0-S1044579X24000361-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141163265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53/MDM2 signaling pathway in aging, senescence and tumorigenesis.","authors":"Youyi Huang, Xiaofang Che, Peter W Wang, Xiujuan Qu","doi":"10.1016/j.semcancer.2024.05.001","DOIUrl":"10.1016/j.semcancer.2024.05.001","url":null,"abstract":"<p><p>A wealth of evidence has emerged that there is an association between aging, senescence and tumorigenesis. Senescence, a biological process by which cells cease to divide and enter a status of permanent cell cycle arrest, contributes to aging and aging-related diseases, including cancer. Aging populations have the higher incidence of cancer due to a lifetime of exposure to cancer-causing agents, reduction of repairing DNA damage, accumulated genetic mutations, and decreased immune system efficiency. Cancer patients undergoing cytotoxic therapies, such as chemotherapy and radiotherapy, accelerate aging. There is growing evidence that p53/MDM2 (murine double minute 2) axis is critically involved in regulation of aging, senescence and oncogenesis. Therefore, in this review, we describe the functions and mechanisms of p53/MDM2-mediated senescence, aging and carcinogenesis. Moreover, we highlight the small molecular inhibitors, natural compounds and PROTACs (proteolysis targeting chimeras) that target p53/MDM2 pathway to influence aging and cancer. Modification of p53/MDM2 could be a potential strategy for treatment of aging, senescence and tumorigenesis.</p>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":" ","pages":"44-57"},"PeriodicalIF":14.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53/MDM2 signaling pathway in aging, senescence and tumorigenesis","authors":"Youyi Huang ,&nbsp;Xiaofang Che ,&nbsp;Peter W. Wang ,&nbsp;Xiujuan Qu","doi":"10.1016/j.semcancer.2024.05.001","DOIUrl":"10.1016/j.semcancer.2024.05.001","url":null,"abstract":"<div><p>A wealth of evidence has emerged that there is an association between aging, senescence and tumorigenesis. Senescence, a biological process by which cells cease to divide and enter a status of permanent cell cycle arrest, contributes to aging and aging-related diseases, including cancer. Aging populations have the higher incidence of cancer due to a lifetime of exposure to cancer-causing agents, reduction of repairing DNA damage, accumulated genetic mutations, and decreased immune system efficiency. Cancer patients undergoing cytotoxic therapies, such as chemotherapy and radiotherapy, accelerate aging. There is growing evidence that p53/MDM2 (murine double minute 2) axis is critically involved in regulation of aging, senescence and oncogenesis. Therefore, in this review, we describe the functions and mechanisms of p53/MDM2-mediated senescence, aging and carcinogenesis. Moreover, we highlight the small molecular inhibitors, natural compounds and PROTACs (proteolysis targeting chimeras) that target p53/MDM2 pathway to influence aging and cancer. Modification of p53/MDM2 could be a potential strategy for treatment of aging, senescence and tumorigenesis.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"101 ","pages":"Pages 44-57"},"PeriodicalIF":14.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141035897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles in glioblastoma: Biomarkers and therapeutic tools","authors":"Ilaria Cela ,&nbsp;Emily Capone ,&nbsp;Gianluca Trevisi ,&nbsp;Gianluca Sala","doi":"10.1016/j.semcancer.2024.04.003","DOIUrl":"10.1016/j.semcancer.2024.04.003","url":null,"abstract":"<div><p>Glioblastoma (GBM) is the most aggressive tumor among the gliomas and intracranial tumors and to date prognosis for GBM patients remains poor, with a median survival typically measured in months to a few years depending on various factors. Although standardized therapies are routinely employed, it is clear that these strategies are unable to cope with heterogeneity and invasiveness of GBM. Furthermore, diagnosis and monitoring of responses to therapies are directly dependent on tissue biopsies or magnetic resonance imaging (MRI) techniques. From this point of view, liquid biopsies are arising as key sources of a variety of biomarkers with the advantage of being easily accessible and monitorable. In this context, extracellular vesicles (EVs), physiologically shed into body fluids by virtually all cells, are gaining increasing interest both as natural carriers of biomarkers and as specific signatures even for GBM. What makes these vesicles particularly attractive is they are also emerging as therapeutical vehicles to treat GBM given their native ability to cross the blood-brain barrier (BBB). Here, we reviewed recent advances on the use of EVs as biomarker for liquid biopsy and nanocarriers for targeted delivery of anticancer drugs in glioblastoma.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"101 ","pages":"Pages 25-43"},"PeriodicalIF":14.5,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X24000348/pdfft?md5=8d0c3ccb77f687de9a64eecf6020aea8&pid=1-s2.0-S1044579X24000348-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141036332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of the minimal information for studies of extracellular vesicles guidelines: Advancements and implications for extracellular vesicle research","authors":"Elisavet Maria Vaiaki,&nbsp;Marco Falasca","doi":"10.1016/j.semcancer.2024.04.002","DOIUrl":"10.1016/j.semcancer.2024.04.002","url":null,"abstract":"<div><p>In 2014, the International Society for Extracellular Vesicles (ISEV) introduced the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines to establish standards for extracellular vesicle (EV) research. These guidelines aimed to enhance reliability and reproducibility, addressing the expanding field of EV science. EVs, membrane-bound particles released by cells, play crucial roles in intercellular communication and are potential biomarkers for various conditions. Over the years, the EV landscape witnessed a surge in publications, emphasizing their roles in cancer and immune modulation. In response, the MISEV guidelines underwent evolution, leading to the MISEV2018 update. This version, generated through community outreach, provided a comprehensive framework for EV research methodologies, emphasizing separation, characterization, reporting standards, and community engagement. The MISEV2018 guidelines reflected responsiveness to feedback, acknowledging the evolving EV research landscape. The guidelines served as a testament to the commitment of the scientific community to rigorous standards and the collective discernment of experts. The present article compares previous MISEV guidelines with its 2023 counterpart, highlighting advancements, changes, and impacts on EV research standardization. The 2023 guidelines build upon the 2018 principles, offering new recommendations for emerging areas. This comparative exploration contributes to understanding the transformative journey in EV research, emphasizing MISEV's pivotal role and the scientific community's adaptability to challenges.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"101 ","pages":"Pages 12-24"},"PeriodicalIF":14.5,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X24000336/pdfft?md5=5d1df6bf520734384dc1f8a2ec67eb1b&pid=1-s2.0-S1044579X24000336-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative splicing in EMT and TGF-β signaling during cancer progression","authors":"Ying E. Zhang,&nbsp;Christina H. Stuelten","doi":"10.1016/j.semcancer.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.semcancer.2024.04.001","url":null,"abstract":"<div><p>Epithelial to mesenchymal transition (EMT) is a physiological process during development where epithelial cells transform to acquire mesenchymal characteristics, which allows them to migrate and colonize secondary tissues. Many cellular signaling pathways and master transcriptional factors exert a myriad of controls to fine tune this vital process to meet various developmental and physiological needs. Adding to the complexity of this network are post-transcriptional and post-translational regulations. Among them, alternative splicing has been shown to play important roles to drive EMT-associated phenotypic changes, including actin cytoskeleton remodeling, cell-cell junction changes, cell motility and invasiveness. In advanced cancers, transforming growth factor-β (TGF-β) is a major inducer of EMT and is associated with tumor cell metastasis, cancer stem cell self-renewal, and drug resistance. This review aims to provide an overview of recent discoveries regarding alternative splicing events and the involvement of splicing factors in the EMT and TGF-β signaling. It will emphasize the importance of various splicing factors involved in EMT and explore their regulatory mechanisms.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"101 ","pages":"Pages 1-11"},"PeriodicalIF":14.5,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140555311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxic adaptation of mitochondria and its impact on tumor cell function","authors":"Martin Benej ,&nbsp;Ioanna Papandreou ,&nbsp;Nicholas C. Denko","doi":"10.1016/j.semcancer.2024.03.004","DOIUrl":"10.1016/j.semcancer.2024.03.004","url":null,"abstract":"<div><p>Mitochondria are the major sink for oxygen in the cell, consuming it during ATP production. Therefore, when environmental oxygen levels drop in the tumor, significant adaptation is required. Mitochondrial activity is also a major producer of biosynthetic precursors and a regulator of cellular oxidative and reductive balance. Because of the complex biochemistry, mitochondrial adaptation to hypoxia occurs through multiple mechanisms and has significant impact on other cellular processes such as macromolecule synthesis and gene regulation. In tumor hypoxia, mitochondria shift their location in the cell and accelerate the fission and quality control pathways. Hypoxic mitochondria also undergo significant changes to fundamental metabolic pathways of carbon metabolism and electron transport. These metabolic changes further impact the nuclear epigenome because mitochondrial metabolites are used as enzymatic substrates for modifying chromatin. This coordinated response delivers physiological flexibility and increased tumor cell robustness during the environmental stress of low oxygen.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"100 ","pages":"Pages 28-38"},"PeriodicalIF":14.5,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X24000221/pdfft?md5=e97fd4671caea21daf3822c0f7a9c5d1&pid=1-s2.0-S1044579X24000221-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}