TTK, also known as MPS1 (the monopolar spindle 1)/ MPS1L1, is located on chromosome 6q13-q21 and encodes a dual-specific protein kinase that phosphorylates serine and threonine [1]. The spindle assembly checkpoint (SAC) plays a key role in mitosis. The SAC acts as a molecular monitoring mechanism, which delays mitosis until all chromosomes are properly attached to the spindle microtubules. As a key regulator of the SAC, TTK plays an important role in controlling cell cycle progression and maintaining genomic integrity [2]. TTK is vital for the recruitment of kinetochore components to unattached kinetochores and is essential for correcting improperly attached chromosomes. Interestingly, TTK is highly expressed in many types of malignant tumors [3]. However, TTK expression is low in most organs, except in the testis and placenta. Once TTK is inhibited, cancer cells exit mitosis prematurely, with more chromosome segregation errors and aneuploids. After several rounds of cell division, the accumulation of chromosome segregation errors may lead to cancer cell death [4]. Therefore, TTK has gradually become a research hotspot for anticancer drugs, and TTK inhibitors are increasingly being investigated in clinical trials.
{"title":"TTK: A Promising Target in Malignant Tumors","authors":"Weiping Yao, Mingyun Jiang, Minjun Zhang, Haibo Zhang, Xiaodong Liang","doi":"10.33696/signaling.2.053","DOIUrl":"https://doi.org/10.33696/signaling.2.053","url":null,"abstract":"TTK, also known as MPS1 (the monopolar spindle 1)/ MPS1L1, is located on chromosome 6q13-q21 and encodes a dual-specific protein kinase that phosphorylates serine and threonine [1]. The spindle assembly checkpoint (SAC) plays a key role in mitosis. The SAC acts as a molecular monitoring mechanism, which delays mitosis until all chromosomes are properly attached to the spindle microtubules. As a key regulator of the SAC, TTK plays an important role in controlling cell cycle progression and maintaining genomic integrity [2]. TTK is vital for the recruitment of kinetochore components to unattached kinetochores and is essential for correcting improperly attached chromosomes. Interestingly, TTK is highly expressed in many types of malignant tumors [3]. However, TTK expression is low in most organs, except in the testis and placenta. Once TTK is inhibited, cancer cells exit mitosis prematurely, with more chromosome segregation errors and aneuploids. After several rounds of cell division, the accumulation of chromosome segregation errors may lead to cancer cell death [4]. Therefore, TTK has gradually become a research hotspot for anticancer drugs, and TTK inhibitors are increasingly being investigated in clinical trials.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91205284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-02DOI: 10.33696/signaling.2.048
C. Warren, M. Halas, H. Feng, B. Wolska, Jian-Ping Jin, R. Solaro
Cardiac sarcomeres express a variant of troponin I (cTnI) that contains a unique N-terminal extension of ~30 amino acids with regulatory phosphorylation sites. The extension is important in the control of myofilament response to Ca2+, which contributes to the neuro-humoral regulation of the dynamics of cardiac contraction and relaxation. Hearts of various species including humans express a stress-induced truncated variant of cardiac troponin I (cTnI-ND) missing the first ~30 amino acids and functionally mimicking the phosphorylated state of cTnI. Studies have demonstrated that upregulation of cTnI-ND potentially represents a homeostatic mechanism as well as an adaptive response in pathophysiology including ischemia/reperfusion injury, beta adrenergic maladaptive activation, and aging. We present evidence showing that cTnI-ND can modify the trigger for hypertrophic cardiomyopathy (HCM) by reducing the Ca2+ sensitivity of myofilaments from hearts with an E180G mutation in α-tropomyosin. Induction of this truncation may represent a therapeutic approach to modifying Ca2+-responses in hearts with hypercontractility or heat failure with preserved ejection fraction.
{"title":"NH2-Terminal Cleavage of Cardiac Troponin I Signals Adaptive Response to Cardiac Stressors","authors":"C. Warren, M. Halas, H. Feng, B. Wolska, Jian-Ping Jin, R. Solaro","doi":"10.33696/signaling.2.048","DOIUrl":"https://doi.org/10.33696/signaling.2.048","url":null,"abstract":"Cardiac sarcomeres express a variant of troponin I (cTnI) that contains a unique N-terminal extension of ~30 amino acids with regulatory phosphorylation sites. The extension is important in the control of myofilament response to Ca2+, which contributes to the neuro-humoral regulation of the dynamics of cardiac contraction and relaxation. Hearts of various species including humans express a stress-induced truncated variant of cardiac troponin I (cTnI-ND) missing the first ~30 amino acids and functionally mimicking the phosphorylated state of cTnI. Studies have demonstrated that upregulation of cTnI-ND potentially represents a homeostatic mechanism as well as an adaptive response in pathophysiology including ischemia/reperfusion injury, beta adrenergic maladaptive activation, and aging. We present evidence showing that cTnI-ND can modify the trigger for hypertrophic cardiomyopathy (HCM) by reducing the Ca2+ sensitivity of myofilaments from hearts with an E180G mutation in α-tropomyosin. Induction of this truncation may represent a therapeutic approach to modifying Ca2+-responses in hearts with hypercontractility or heat failure with preserved ejection fraction.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"10 1","pages":"162 - 171"},"PeriodicalIF":0.0,"publicationDate":"2021-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81263147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.33696/signaling.2.049
Gabrielle Westenberger, Jacob Sellers, Savanie Fernando, S. Junkins, S. Han, Kisuk Min, A. Lawan
The western diet and overuse of anti-inflammatory medication have caused a great deal of stress on the liver. Obesity and the associated inflammatory state in insulin-responsive tissues result in the release of pro-inflammatory cytokine that activates the stress-responsive MAPKs, p38 MAPK, and JNK. These MAPKs have figured prominently as critical effectors in physiological and pathophysiological hepatic inflammation. In contrast, evidence for a role for ERK1/2 in hepatic inflammation has been less well developed. In this review article, we describe recent insights into the physiology and pathophysiology of the role of stress-responsive MAPKs in hepatic inflammation during obesity and liver injury with a focus on macrophages, hepatocytes and hepatic stellate cells. In response to metabolic stress and liver injury, JNK activation in macrophages and hepatocytes promotes the secretion of inflammatory cytokines and macrophage and neutrophil infiltration. p38 MAPK plays an important role in contributing to the progression of hepatic inflammation in response to various hepatic cellular stresses, although the precise substrates mediating these effects in hepatocytes and hepatic stellate cells remain to be identified. Both JNK and p38 MAPK promotes profibrotic behavior in hepatic stellate cells.
{"title":"Function of Mitogen-Activated Protein Kinases in Hepatic Inflammation","authors":"Gabrielle Westenberger, Jacob Sellers, Savanie Fernando, S. Junkins, S. Han, Kisuk Min, A. Lawan","doi":"10.33696/signaling.2.049","DOIUrl":"https://doi.org/10.33696/signaling.2.049","url":null,"abstract":"The western diet and overuse of anti-inflammatory medication have caused a great deal of stress on the liver. Obesity and the associated inflammatory state in insulin-responsive tissues result in the release of pro-inflammatory cytokine that activates the stress-responsive MAPKs, p38 MAPK, and JNK. These MAPKs have figured prominently as critical effectors in physiological and pathophysiological hepatic inflammation. In contrast, evidence for a role for ERK1/2 in hepatic inflammation has been less well developed. In this review article, we describe recent insights into the physiology and pathophysiology of the role of stress-responsive MAPKs in hepatic inflammation during obesity and liver injury with a focus on macrophages, hepatocytes and hepatic stellate cells. In response to metabolic stress and liver injury, JNK activation in macrophages and hepatocytes promotes the secretion of inflammatory cytokines and macrophage and neutrophil infiltration. p38 MAPK plays an important role in contributing to the progression of hepatic inflammation in response to various hepatic cellular stresses, although the precise substrates mediating these effects in hepatocytes and hepatic stellate cells remain to be identified. Both JNK and p38 MAPK promotes profibrotic behavior in hepatic stellate cells.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"29 1","pages":"172 - 180"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83501677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-08-01DOI: 10.33696/signaling.2.047
M. Mijit, R. Caston, S. Gampala, M. Fishel, J. Fehrenbacher, M. Kelley
In the realm of DNA repair, base excision repair (BER) protein, APE1/Ref-1 (Apurinic/Apyrimidinic Endonuclease 1/Redox Effector - 1, also called APE1) has been studied for decades. However, over the past decade, APE1 has been established as a key player in reduction-oxidation (redox) signaling. In the review by Caston et al. (The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease), multiple roles of APE1 in cancer and other diseases are summarized. In this Review, we aim to expand on the contributions of APE1 to various diseases and its effect on disease progression. In the scope of cancer, more recent roles for APE1 have been identified in cancer cell metabolism, as well as chemotherapy-induced peripheral neuropathy (CIPN) and inflammation. Outside of cancer, APE1 signaling may be a critical factor in inflammatory bowel disease (IBD) and is also an emergent area of investigation in retinal ocular diseases. The ability of APE1 to regulate multiple transcription factors (TFs) and therefore multiple pathways that have implications outside of cancer, makes it a particularly unique and enticing target. We discuss APE1 redox inhibitors as a means of studying and potentially combating these diseases. Lastly, we examine the role of APE1 in RNA metabolism. Overall, this article builds on our previous review to elaborate on the roles and conceivable regulation of important pathways by APE1 in multiple diseases.
在DNA修复领域，碱基切除修复(BER)蛋白APE1/Ref-1(无嘌呤/无嘧啶内切酶1/氧化还原效应-1，也称为APE1)已经研究了几十年。然而，在过去的十年中，APE1已被确定为还原-氧化(氧化还原)信号传导的关键角色。在Caston等人(the multifunctional APE1 DNA repair-redox signaling protein as a drug target In human disease)的综述中，总结了APE1在癌症等疾病中的多重作用。在这篇综述中，我们旨在扩大APE1在各种疾病中的作用及其对疾病进展的影响。在癌症的范围内，APE1最近在癌细胞代谢，以及化疗诱导的周围神经病变(CIPN)和炎症中的作用已被确定。在癌症之外，APE1信号可能是炎症性肠病(IBD)的一个关键因素，也是视网膜眼部疾病的一个新兴研究领域。APE1调节多种转录因子(TFs)的能力，从而影响癌症以外的多种途径，使其成为一个特别独特和诱人的靶标。我们讨论了APE1氧化还原抑制剂作为研究和潜在对抗这些疾病的手段。最后，我们研究了APE1在RNA代谢中的作用。总之，本文建立在我们之前的综述的基础上，详细阐述了APE1在多种疾病中重要途径的作用和可能的调控。
{"title":"APE1/Ref-1 – One Target with Multiple Indications: Emerging Aspects and New Directions","authors":"M. Mijit, R. Caston, S. Gampala, M. Fishel, J. Fehrenbacher, M. Kelley","doi":"10.33696/signaling.2.047","DOIUrl":"https://doi.org/10.33696/signaling.2.047","url":null,"abstract":"In the realm of DNA repair, base excision repair (BER) protein, APE1/Ref-1 (Apurinic/Apyrimidinic Endonuclease 1/Redox Effector - 1, also called APE1) has been studied for decades. However, over the past decade, APE1 has been established as a key player in reduction-oxidation (redox) signaling. In the review by Caston et al. (The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease), multiple roles of APE1 in cancer and other diseases are summarized. In this Review, we aim to expand on the contributions of APE1 to various diseases and its effect on disease progression. In the scope of cancer, more recent roles for APE1 have been identified in cancer cell metabolism, as well as chemotherapy-induced peripheral neuropathy (CIPN) and inflammation. Outside of cancer, APE1 signaling may be a critical factor in inflammatory bowel disease (IBD) and is also an emergent area of investigation in retinal ocular diseases. The ability of APE1 to regulate multiple transcription factors (TFs) and therefore multiple pathways that have implications outside of cancer, makes it a particularly unique and enticing target. We discuss APE1 redox inhibitors as a means of studying and potentially combating these diseases. Lastly, we examine the role of APE1 in RNA metabolism. Overall, this article builds on our previous review to elaborate on the roles and conceivable regulation of important pathways by APE1 in multiple diseases.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"68 1","pages":"151 - 161"},"PeriodicalIF":0.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72652074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.33696/signaling.2.043
Aaran Vijayakumaran, M. Tavassoli
Head and neck squamous cell carcinomas (HNSCCs) are a heterogeneous group of aggressive malignancies strongly linked with chronic tobacco exposure, excessive alcohol consumption, and infection with high-risk subtypes of Human Papilloma Virus (HPV). Molecularly, HNSCC is classified into HPV-positive and HPV-negative sub-types [1]. Approximately 600,000 new cases are diagnosed annually with 380,000 deaths worldwide [2]. Despite our increased understanding of the viral and genetic mechanisms underlying HNSCC, the 5-year overall survival rate remains around 50% [3]. Radiotherapy (RT), chemotherapy (CT), surgical eradication, or a combination of all modalities are the current therapeutic options but are highly toxic and cause psychological distress and severely compromised quality of life, and hence associated with both symptomology and treatment survivors of this cancer have the second-highest mortality rate of suicide (63.4 per 100,000; [2000-2014]) [4]. The functional and aesthetic features of the head and neck anatomy are factors that make HNSCCs difficult to treat as tumours are located nearby critical anatomical structures which are sensitive to treatment. Radiotherapy (RT), chemotherapy (CT), surgical eradication, or a combination of all modalities are the current therapeutic options. Cetuximab is a monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) and has been the only targeted FDA approved targeted therapy for HNSCC until the recent FDA approval of immunotherapy, but, both Cetuximab and immunotherapy clinical efficacy for HNSCC has been limited [5].
{"title":"HGF/MET Signalling and DNA Damage Response: Strategies to Conquer Radiotherapy Resistance in Head and Neck Cancer","authors":"Aaran Vijayakumaran, M. Tavassoli","doi":"10.33696/signaling.2.043","DOIUrl":"https://doi.org/10.33696/signaling.2.043","url":null,"abstract":"Head and neck squamous cell carcinomas (HNSCCs) are a heterogeneous group of aggressive malignancies strongly linked with chronic tobacco exposure, excessive alcohol consumption, and infection with high-risk subtypes of Human Papilloma Virus (HPV). Molecularly, HNSCC is classified into HPV-positive and HPV-negative sub-types [1]. Approximately 600,000 new cases are diagnosed annually with 380,000 deaths worldwide [2]. Despite our increased understanding of the viral and genetic mechanisms underlying HNSCC, the 5-year overall survival rate remains around 50% [3]. Radiotherapy (RT), chemotherapy (CT), surgical eradication, or a combination of all modalities are the current therapeutic options but are highly toxic and cause psychological distress and severely compromised quality of life, and hence associated with both symptomology and treatment survivors of this cancer have the second-highest mortality rate of suicide (63.4 per 100,000; [2000-2014]) [4]. The functional and aesthetic features of the head and neck anatomy are factors that make HNSCCs difficult to treat as tumours are located nearby critical anatomical structures which are sensitive to treatment. Radiotherapy (RT), chemotherapy (CT), surgical eradication, or a combination of all modalities are the current therapeutic options. Cetuximab is a monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) and has been the only targeted FDA approved targeted therapy for HNSCC until the recent FDA approval of immunotherapy, but, both Cetuximab and immunotherapy clinical efficacy for HNSCC has been limited [5].","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83399775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.33696/signaling.2.040
R. Yamaguchi, Y. Yamaguchi
Ectodomain shedding mediated by a disintegrin and metalloprotease 10/17 (ADAM10/17) modulates the function of immune effector cells and may be involved in the novel coronavirus disease COVID-19. Toll-like receptor 7/8 (TLR7/8) recognizes single-strand RNA from viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19) during the innate immune response [1], and TLR7/8 agonist activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate reactive oxygen species (ROS) [2]. ADAM10/7 was found to mediate ectodomain shedding to modulate immune responses [3] and to be activated by ROS [4]. These findings suggest that SARS-CoV-2 contributes to and induces ectodomain shedding, which may be associated with disease severity. In patients with COVID-19, studies found a higher blood concentration of the chemokine fractalkine [5]. Cell membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified as a binding site and entry receptor for the spike protein of SARS-CoV-2. After the
{"title":"Ectodomain Shedding May Play a Pivotal Role in Disease Severity in COVID-19","authors":"R. Yamaguchi, Y. Yamaguchi","doi":"10.33696/signaling.2.040","DOIUrl":"https://doi.org/10.33696/signaling.2.040","url":null,"abstract":"Ectodomain shedding mediated by a disintegrin and metalloprotease 10/17 (ADAM10/17) modulates the function of immune effector cells and may be involved in the novel coronavirus disease COVID-19. Toll-like receptor 7/8 (TLR7/8) recognizes single-strand RNA from viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19) during the innate immune response [1], and TLR7/8 agonist activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate reactive oxygen species (ROS) [2]. ADAM10/7 was found to mediate ectodomain shedding to modulate immune responses [3] and to be activated by ROS [4]. These findings suggest that SARS-CoV-2 contributes to and induces ectodomain shedding, which may be associated with disease severity. In patients with COVID-19, studies found a higher blood concentration of the chemokine fractalkine [5]. Cell membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified as a binding site and entry receptor for the spike protein of SARS-CoV-2. After the","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78325224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.33696/signaling.2.042
Vitor C. Neves, Jing Zhao, A. Caetano, P. Sharpe
The balance between cell removal following tissue damage and new cell formation to facilitate repair has long been linked to the behaviour of inflammatory macrophages and their interactions with tissue-resident non-immune cells. The main aim of the inflammatory response is to modulate the tissue environment by removing unwanted cells and recruiting cells and soluble factors from the bloodstream to help protect the damaged tissue against infective foreign bodies. Such processes are essential for remodeling, repair, and forming new tissue in the area of damage. Macrophages play an important role in tissue repair and regeneration by exerting their effects in various tissue repair and regeneration effects by exerting their effects in various tissue repair and regeneration effects by exerting their marks in multiple ways during these processes. Current research shows that depletion of macrophages is detrimental for skin and muscle repair and whole limb regeneration [1-3]. Moreover, resident macrophages are described as regulators of inflammation levels by ‘cloaking’ microinjuries and regulating neutrophil recruitment [4-5].
{"title":"Macrophages in Oral Tissues","authors":"Vitor C. Neves, Jing Zhao, A. Caetano, P. Sharpe","doi":"10.33696/signaling.2.042","DOIUrl":"https://doi.org/10.33696/signaling.2.042","url":null,"abstract":"The balance between cell removal following tissue damage and new cell formation to facilitate repair has long been linked to the behaviour of inflammatory macrophages and their interactions with tissue-resident non-immune cells. The main aim of the inflammatory response is to modulate the tissue environment by removing unwanted cells and recruiting cells and soluble factors from the bloodstream to help protect the damaged tissue against infective foreign bodies. Such processes are essential for remodeling, repair, and forming new tissue in the area of damage. Macrophages play an important role in tissue repair and regeneration by exerting their effects in various tissue repair and regeneration effects by exerting their effects in various tissue repair and regeneration effects by exerting their marks in multiple ways during these processes. Current research shows that depletion of macrophages is detrimental for skin and muscle repair and whole limb regeneration [1-3]. Moreover, resident macrophages are described as regulators of inflammation levels by ‘cloaking’ microinjuries and regulating neutrophil recruitment [4-5].","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77699559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.33696/signaling.2.039
G. Zakiryanova, M. Shurin
Natural Killer (NK) cells play a key role in the immune responses against infection and cancer as powerful cytotoxic effector cells and regulators of both innate and adaptive immunity [1,2]. Therefore, defects in NK cell functions are important mechanisms for immune evasion of malignant cells [3]. For instance, the ability of tumor cells and tumor-associated stromal/infiltrating cells to inhibit NK cell activity, which results in preventing NK cells from recognizing and killing tumor cells, has been reported for melanoma, neuroblastoma, gastrointestinal sarcoma, hepatocellular cancer (HCC), pancreatic cancer, colorectal carcinoma and other types of cancer [4-9]. A potential loss of NK cell numbers and function at preneoplastic stages of tumorigenesis as a possible mechanism for cancer induction and progression has been also recently proposed [5,10]. However, molecular mechanisms regulating NK cell dysfunction and exhaustion in cancer are largely unclear.
{"title":"Cancer-associated Molecular Abnormalities in Human NK cells","authors":"G. Zakiryanova, M. Shurin","doi":"10.33696/signaling.2.039","DOIUrl":"https://doi.org/10.33696/signaling.2.039","url":null,"abstract":"Natural Killer (NK) cells play a key role in the immune responses against infection and cancer as powerful cytotoxic effector cells and regulators of both innate and adaptive immunity [1,2]. Therefore, defects in NK cell functions are important mechanisms for immune evasion of malignant cells [3]. For instance, the ability of tumor cells and tumor-associated stromal/infiltrating cells to inhibit NK cell activity, which results in preventing NK cells from recognizing and killing tumor cells, has been reported for melanoma, neuroblastoma, gastrointestinal sarcoma, hepatocellular cancer (HCC), pancreatic cancer, colorectal carcinoma and other types of cancer [4-9]. A potential loss of NK cell numbers and function at preneoplastic stages of tumorigenesis as a possible mechanism for cancer induction and progression has been also recently proposed [5,10]. However, molecular mechanisms regulating NK cell dysfunction and exhaustion in cancer are largely unclear.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91012926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-18DOI: 10.33696/SIGNALING.2.036
Nabab Khan, Xuesong Chen, J. Geiger
The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to coronavirus disease-19 (COVID-19); a pandemic disease that has resulted in devastating social, economic, morbidity and mortality burdens. SARS-CoV-2 infects cells following receptor-mediated endocytosis and priming by cellular proteases. Following uptake, SARS-CoV-2 replicates in autophagosome-like structures in the cytosol following its escape from endolysosomes. Accordingly, the greater endolysosome pathway including autophagosomes and the mTOR sensor may be targets for therapeutic interventions against SARS-CoV-2 infection and COVID-19 pathogenesis. Naturally existing compounds (phytochemicals) through their actions on endolysosomes and mTOR signaling pathways might provide therapeutic relief against COVID-19. Here, we discuss evidence that some natural compounds through actions on the greater endolysosome system can inhibit SARS-CoV-2 infectivity and thereby might be repurposed for use against COVID-19.
{"title":"Possible Therapeutic Use of Natural Compounds Against COVID-19","authors":"Nabab Khan, Xuesong Chen, J. Geiger","doi":"10.33696/SIGNALING.2.036","DOIUrl":"https://doi.org/10.33696/SIGNALING.2.036","url":null,"abstract":"The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to coronavirus disease-19 (COVID-19); a pandemic disease that has resulted in devastating social, economic, morbidity and mortality burdens. SARS-CoV-2 infects cells following receptor-mediated endocytosis and priming by cellular proteases. Following uptake, SARS-CoV-2 replicates in autophagosome-like structures in the cytosol following its escape from endolysosomes. Accordingly, the greater endolysosome pathway including autophagosomes and the mTOR sensor may be targets for therapeutic interventions against SARS-CoV-2 infection and COVID-19 pathogenesis. Naturally existing compounds (phytochemicals) through their actions on endolysosomes and mTOR signaling pathways might provide therapeutic relief against COVID-19. Here, we discuss evidence that some natural compounds through actions on the greater endolysosome system can inhibit SARS-CoV-2 infectivity and thereby might be repurposed for use against COVID-19.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"13 1","pages":"63 - 79"},"PeriodicalIF":0.0,"publicationDate":"2021-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89330314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-02DOI: 10.33696/SIGNALING.2.034
J. Joshi, Bhagwati Joshi, Ian Rochford, D. Mehta
Acute respiratory distress syndrome (ARDS) is the major cause of mortality among hospitalized acute lung injury (ALI) patients. Lung macrophages play an important role in maintaining the tissue-fluid homeostasis following injury. We recently showed that circulating monocytes recruited into the alveolar space suppressed the stimulator of type 1 interferon genes (STING) signaling in alveolar macrophages through sphingosine-1-phosphate (S1P). We used CD11b-DTR mice to deplete CD11b+ monocytes following LPS or Pseudomonas aeruginosa infection. Depletion of CD11b+ monocytes leads to the persistent inflammatory injury, infiltration of neutrophils, activation of STING signaling and mortality following lung infection. We demonstrated that adoptively transferred SPHK2-CD11b+ monocytes into CD11b-DTR mice after pathogenic infection rescue lung inflammatory injury.
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