Jessica Parker, Sean Hockney, Orest W Blaschuk, Deepali Pal
This review discusses current research on acute paediatric leukaemia, the leukaemic bone marrow (BM) microenvironment and recently discovered therapeutic opportunities to target leukaemia-niche interactions. The tumour microenvironment plays an integral role in conferring treatment resistance to leukaemia cells, this poses as a key clinical challenge that hinders management of this disease. Here we focus on the role of the cell adhesion molecule N-cadherin (CDH2) within the malignant BM microenvironment and associated signalling pathways that may bear promise as therapeutic targets. Additionally, we discuss microenvironment-driven treatment resistance and relapse, and elaborate the role of CDH2-mediated cancer cell protection from chemotherapy. Finally, we review emerging therapeutic approaches that directly target CDH2-mediated adhesive interactions between the BM cells and leukaemia cells.
{"title":"Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia.","authors":"Jessica Parker, Sean Hockney, Orest W Blaschuk, Deepali Pal","doi":"10.1017/erm.2023.13","DOIUrl":"https://doi.org/10.1017/erm.2023.13","url":null,"abstract":"<p><p>This review discusses current research on acute paediatric leukaemia, the leukaemic bone marrow (BM) microenvironment and recently discovered therapeutic opportunities to target leukaemia-niche interactions. The tumour microenvironment plays an integral role in conferring treatment resistance to leukaemia cells, this poses as a key clinical challenge that hinders management of this disease. Here we focus on the role of the cell adhesion molecule N-cadherin (CDH2) within the malignant BM microenvironment and associated signalling pathways that may bear promise as therapeutic targets. Additionally, we discuss microenvironment-driven treatment resistance and relapse, and elaborate the role of CDH2-mediated cancer cell protection from chemotherapy. Finally, we review emerging therapeutic approaches that directly target CDH2-mediated adhesive interactions between the BM cells and leukaemia cells.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e16"},"PeriodicalIF":6.2,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10317925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"25 years of <i>ERMM</i>.","authors":"Nicola Curtin","doi":"10.1017/erm.2023.8","DOIUrl":"https://doi.org/10.1017/erm.2023.8","url":null,"abstract":"","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e12"},"PeriodicalIF":6.2,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10317905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexa Little, Mark Tangney, Michael M Tunney, Niamh E Buckley
Breast cancer was the most commonly diagnosed cancer worldwide in 2020. Greater understanding of the factors which promote tumour progression, metastatic development and therapeutic resistance is needed. In recent years, a distinct microbiome has been detected in the breast, a site previously thought to be sterile. Here, we review the clinical and molecular relevance of the oral anaerobic bacterium Fusobacterium nucleatum in breast cancer. F. nucleatum is enriched in breast tumour tissue compared with matched healthy tissue and has been shown to promote mammary tumour growth and metastatic progression in mouse models. Current literature suggests that F. nucleatum modulates immune escape and inflammation within the tissue microenvironment, two well-defined hallmarks of cancer. Furthermore, the microbiome, and F. nucleatum specifically, has been shown to affect patient response to therapy including immune checkpoint inhibitors. These findings highlight areas of future research needed to better understand the influence of F. nucleatum in the development and treatment of breast cancer.
{"title":"<i>Fusobacterium nucleatum</i>: a novel immune modulator in breast cancer?","authors":"Alexa Little, Mark Tangney, Michael M Tunney, Niamh E Buckley","doi":"10.1017/erm.2023.9","DOIUrl":"https://doi.org/10.1017/erm.2023.9","url":null,"abstract":"<p><p>Breast cancer was the most commonly diagnosed cancer worldwide in 2020. Greater understanding of the factors which promote tumour progression, metastatic development and therapeutic resistance is needed. In recent years, a distinct microbiome has been detected in the breast, a site previously thought to be sterile. Here, we review the clinical and molecular relevance of the oral anaerobic bacterium <i>Fusobacterium nucleatum</i> in breast cancer. <i>F. nucleatum</i> is enriched in breast tumour tissue compared with matched healthy tissue and has been shown to promote mammary tumour growth and metastatic progression in mouse models. Current literature suggests that <i>F. nucleatum</i> modulates immune escape and inflammation within the tissue microenvironment, two well-defined hallmarks of cancer. Furthermore, the microbiome, and <i>F. nucleatum</i> specifically, has been shown to affect patient response to therapy including immune checkpoint inhibitors. These findings highlight areas of future research needed to better understand the influence of <i>F. nucleatum</i> in the development and treatment of breast cancer.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e15"},"PeriodicalIF":6.2,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10016299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they might be connected to both aging and the onset and progression of disease. Additionally, we go over the most recent preclinical data supporting the use of autophagy modulators as age-related illnesses including cancer, cardiovascular and neurodegenerative diseases, and metabolic dysfunction. It is crucial to discover important targets in the autophagy pathway in order to create innovative therapies that effectively target autophagy. Natural products have pharmacological properties that can be therapeutically advantageous for the treatment of several diseases and they also serve as valuable sources of inspiration for the development of possible new small-molecule drugs. Indeed, recent scientific studies have shown that several natural products including alkaloids, terpenoids, steroids, and phenolics, have the ability to alter a number of important autophagic signalling pathways and exert therapeutic effects, thus, a wide range of potential targets in various stages of autophagy have been discovered. In this review, we summarised the naturally occurring active compounds that may control the autophagic signalling pathways.
{"title":"Autophagic mechanisms in longevity intervention: role of natural active compounds.","authors":"Kevser Taban Akça, İlknur Çınar Ayan, Sümeyra Çetinkaya, Ece Miser Salihoğlu, İpek Süntar","doi":"10.1017/erm.2023.5","DOIUrl":"https://doi.org/10.1017/erm.2023.5","url":null,"abstract":"<p><p>The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they might be connected to both aging and the onset and progression of disease. Additionally, we go over the most recent preclinical data supporting the use of autophagy modulators as age-related illnesses including cancer, cardiovascular and neurodegenerative diseases, and metabolic dysfunction. It is crucial to discover important targets in the autophagy pathway in order to create innovative therapies that effectively target autophagy. Natural products have pharmacological properties that can be therapeutically advantageous for the treatment of several diseases and they also serve as valuable sources of inspiration for the development of possible new small-molecule drugs. Indeed, recent scientific studies have shown that several natural products including alkaloids, terpenoids, steroids, and phenolics, have the ability to alter a number of important autophagic signalling pathways and exert therapeutic effects, thus, a wide range of potential targets in various stages of autophagy have been discovered. In this review, we summarised the naturally occurring active compounds that may control the autophagic signalling pathways.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e13"},"PeriodicalIF":6.2,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9953628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Sell, Charmaine A Ramlogan-Steel, Jason C Steel, Bijay P Dhungel
Cancer metastasis is the primary cause of cancer-related deaths. The seeding of primary tumours at a secondary site is a highly inefficient process requiring substantial alterations in the genetic architecture of cancer cells. These alterations include significant changes in global gene expression patterns. MicroRNAs are small, non-protein coding RNAs which play a central role in regulating gene expression. Here, we focus on microRNA determinants of cancer metastasis and examine microRNA dysregulation in metastatic cancer cells. We dissect the metastatic process in a step-wise manner and summarise the involvement of microRNAs at each step. We also discuss the advantages and limitations of different microRNA-based strategies that have been used to target metastasis in pre-clinical models. Finally, we highlight current clinical trials that use microRNA-based therapies to target advanced or metastatic tumours.
{"title":"MicroRNAs in cancer metastasis: biological and therapeutic implications.","authors":"Marie Sell, Charmaine A Ramlogan-Steel, Jason C Steel, Bijay P Dhungel","doi":"10.1017/erm.2023.7","DOIUrl":"https://doi.org/10.1017/erm.2023.7","url":null,"abstract":"<p><p>Cancer metastasis is the primary cause of cancer-related deaths. The seeding of primary tumours at a secondary site is a highly inefficient process requiring substantial alterations in the genetic architecture of cancer cells. These alterations include significant changes in global gene expression patterns. MicroRNAs are small, non-protein coding RNAs which play a central role in regulating gene expression. Here, we focus on microRNA determinants of cancer metastasis and examine microRNA dysregulation in metastatic cancer cells. We dissect the metastatic process in a step-wise manner and summarise the involvement of microRNAs at each step. We also discuss the advantages and limitations of different microRNA-based strategies that have been used to target metastasis in pre-clinical models. Finally, we highlight current clinical trials that use microRNA-based therapies to target advanced or metastatic tumours.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e14"},"PeriodicalIF":6.2,"publicationDate":"2023-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Quintino Giorgio D'Alessandris, Marco Battistelli, Giovanni Pennisi, Martina Offi, Maurizio Martini, Tonia Cenci, Maria Laura Falchetti, Liverana Lauretti, Alessandro Olivi, Roberto Pallini, Nicola Montano
Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in in vitro and in vivo settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.
{"title":"Telomerase inhibition in malignant gliomas: a systematic review.","authors":"Quintino Giorgio D'Alessandris, Marco Battistelli, Giovanni Pennisi, Martina Offi, Maurizio Martini, Tonia Cenci, Maria Laura Falchetti, Liverana Lauretti, Alessandro Olivi, Roberto Pallini, Nicola Montano","doi":"10.1017/erm.2023.6","DOIUrl":"https://doi.org/10.1017/erm.2023.6","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in <i>in vitro</i> and <i>in vivo</i> settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e10"},"PeriodicalIF":6.2,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9292208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Head and neck squamous cell carcinoma (HNSCC) represents frequent yet aggressive tumours that encompass complex ecosystems of stromal and neoplastic components including a dynamic population of cancer stem cells (CSCs). Recently, research in the field of CSCs has gained increased momentum owing in part to their role in tumourigenicity, metastasis, therapy resistance and relapse. We provide herein a comprehensive assessment of the latest progress in comprehending CSC plasticity, including newly discovered influencing factors and their possible application in HNSCC. We further discuss the dynamic interplay of CSCs within tumour microenvironment considering our evolving appreciation of the contribution of oral microbiota and the pressing need for relevant models depicting their features. In sum, CSCs and tumour plasticity represent an exciting and expanding battleground with great implications for cancer therapy that are only beginning to be appreciated in head and neck oncology.
{"title":"Identity matters: cancer stem cells and tumour plasticity in head and neck squamous cell carcinoma.","authors":"Abdelhakim Salem, Tuula Salo","doi":"10.1017/erm.2023.4","DOIUrl":"https://doi.org/10.1017/erm.2023.4","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) represents frequent yet aggressive tumours that encompass complex ecosystems of stromal and neoplastic components including a dynamic population of cancer stem cells (CSCs). Recently, research in the field of CSCs has gained increased momentum owing in part to their role in tumourigenicity, metastasis, therapy resistance and relapse. We provide herein a comprehensive assessment of the latest progress in comprehending CSC plasticity, including newly discovered influencing factors and their possible application in HNSCC. We further discuss the dynamic interplay of CSCs within tumour microenvironment considering our evolving appreciation of the contribution of oral microbiota and the pressing need for relevant models depicting their features. In sum, CSCs and tumour plasticity represent an exciting and expanding battleground with great implications for cancer therapy that are only beginning to be appreciated in head and neck oncology.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e8"},"PeriodicalIF":6.2,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9483145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.
{"title":"Efficacy of immune checkpoint inhibitor monotherapy or combined with other small molecule-targeted agents in ovarian cancer.","authors":"Munawaer Muaibati, Abasi Abuduyilimu, Tao Zhang, Yun Dai, Ruyuan Li, Fanwei Huang, Kexin Li, Qing Tong, Xiaoyuan Huang, Liang Zhuang","doi":"10.1017/erm.2023.3","DOIUrl":"https://doi.org/10.1017/erm.2023.3","url":null,"abstract":"<p><p>Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e6"},"PeriodicalIF":6.2,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10826404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camila S Padilha, Mehdi Kushkestani, Liliana P Baptista, Karsten Krüger, Fábio Santos Lira
Life expectancy has increased exponentially in the last century accompanied by disability, poor quality of life, and all-cause mortality in older age due to the high prevalence of obesity and physical inactivity in older people. Biologically, the aging process reduces the cell's metabolic and functional efficiency, and disrupts the cell's anabolic and catabolic homeostasis, predisposing older people to many dysfunctional conditions such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. In the immune system, aging also alters cells' metabolic and functional efficiency, a process known as 'immunosenescence', where cells become more broadly inflammatory and their functionality is altered. Notably, autophagy, the conserved and important cellular process that maintains the cell's efficiency and functional homeostasis may protect the immune system from age-associated dysfunctional changes by regulating cell death in activated CD4+ T cells. This regulatory process increases the delivery of the dysfunctional cytoplasmic material to lysosomal degradation while increasing cytokine production, proliferation, and differentiation of CD4+ T cell-mediated immune responses. Poor proliferation and diminished responsiveness to cytokines appear to be ubiquitous features of aged T cells and may explain the delayed peak in T cell expansion and cytotoxic activity commonly observed in the 'immunosenescence' phenotype in the elderly. On the other hand, physical exercise stimulates the expression of crucial nutrient sensors and inhibits the mechanistic target of the rapamycin (mTOR) signaling cascade which increases autophagic activity in cells. Therefore, in this perspective review, we will first contextualize the overall view of the autophagy process and then, we will discuss how body adiposity and physical fitness may counteract autophagy in naïve CD4+ T cells in aging.
{"title":"Autophagy of naïve CD4<sup>+</sup> T cells in aging - the role of body adiposity and physical fitness.","authors":"Camila S Padilha, Mehdi Kushkestani, Liliana P Baptista, Karsten Krüger, Fábio Santos Lira","doi":"10.1017/erm.2023.2","DOIUrl":"https://doi.org/10.1017/erm.2023.2","url":null,"abstract":"<p><p>Life expectancy has increased exponentially in the last century accompanied by disability, poor quality of life, and all-cause mortality in older age due to the high prevalence of obesity and physical inactivity in older people. Biologically, the aging process reduces the cell's metabolic and functional efficiency, and disrupts the cell's anabolic and catabolic homeostasis, predisposing older people to many dysfunctional conditions such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. In the immune system, aging also alters cells' metabolic and functional efficiency, a process known as 'immunosenescence', where cells become more broadly inflammatory and their functionality is altered. Notably, autophagy, the conserved and important cellular process that maintains the cell's efficiency and functional homeostasis may protect the immune system from age-associated dysfunctional changes by regulating cell death in activated CD4+ T cells. This regulatory process increases the delivery of the dysfunctional cytoplasmic material to lysosomal degradation while increasing cytokine production, proliferation, and differentiation of CD4+ T cell-mediated immune responses. Poor proliferation and diminished responsiveness to cytokines appear to be ubiquitous features of aged T cells and may explain the delayed peak in T cell expansion and cytotoxic activity commonly observed in the 'immunosenescence' phenotype in the elderly. On the other hand, physical exercise stimulates the expression of crucial nutrient sensors and inhibits the mechanistic target of the rapamycin (mTOR) signaling cascade which increases autophagic activity in cells. Therefore, in this perspective review, we will first contextualize the overall view of the autophagy process and then, we will discuss how body adiposity and physical fitness may counteract autophagy in naïve CD4+ T cells in aging.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e9"},"PeriodicalIF":6.2,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9482639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Histone lactylation, an indicator of lactate level and glycolysis, has intrinsic connections with cell metabolism that represents a novel epigenetic code affecting the fate of cells including carcinogenesis. Through delineating the relationship between histone lactylation and cancer hallmarks, we propose histone lactylation as a novel epigenetic code priming cells toward the malignant state, and advocate the importance of identifying novel therapeutic strategies or dual-targeting modalities against lactylation toward effective cancer control. This review underpins important yet less-studied area in histone lactylation, and sheds insights on its clinical impact as well as possible therapeutic tools targeting lactylation.
{"title":"Lactate, histone lactylation and cancer hallmarks.","authors":"Xinyu Lv, Yingying Lv, Xiaofeng Dai","doi":"10.1017/erm.2022.42","DOIUrl":"https://doi.org/10.1017/erm.2022.42","url":null,"abstract":"<p><p>Histone lactylation, an indicator of lactate level and glycolysis, has intrinsic connections with cell metabolism that represents a novel epigenetic code affecting the fate of cells including carcinogenesis. Through delineating the relationship between histone lactylation and cancer hallmarks, we propose histone lactylation as a novel epigenetic code priming cells toward the malignant state, and advocate the importance of identifying novel therapeutic strategies or dual-targeting modalities against lactylation toward effective cancer control. This review underpins important yet less-studied area in histone lactylation, and sheds insights on its clinical impact as well as possible therapeutic tools targeting lactylation.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"25 ","pages":"e7"},"PeriodicalIF":6.2,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9077197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}