Cell Communication and Signaling最新文献

{"title":"Chemoresistance and the tumor microenvironment: the critical role of cell-cell communication.","authors":"Bartosz Wilczyński, Alicja Dąbrowska, Julita Kulbacka, Dagmara Baczyńska","doi":"10.1186/s12964-024-01857-7","DOIUrl":"10.1186/s12964-024-01857-7","url":null,"abstract":"<p><p>Resistance of cancer cells to anticancer drugs remains a major challenge in modern medicine. Understanding the mechanisms behind the development of chemoresistance is key to developing appropriate therapies to counteract it. Nowadays, with advances in technology, we are paying more and more attention to the role of the tumor microenvironment (TME) and intercellular interactions in this process. We also know that important elements of the TME are not only the tumor cells themselves but also other cell types, such as mesenchymal stem cells, cancer-associated fibroblasts, stromal cells, and macrophages. TME elements can communicate with each other indirectly (via cytokines, chemokines, growth factors, and extracellular vesicles [EVs]) and directly (via gap junctions, ligand-receptor pairs, cell adhesion, and tunnel nanotubes). This communication appears to be critical for the development of chemoresistance. EVs seem to be particularly interesting structures in this regard. Within these structures, lipids, proteins, and nucleic acids can be transported, acting as signaling molecules that interact with numerous biochemical pathways, thereby contributing to chemoresistance. Moreover, drug efflux pumps, which are responsible for removing drugs from cancer cells, can also be transported via EVs.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"486"},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402069","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":"Targeting mutant p53: a key player in breast cancer pathogenesis and beyond.","authors":"Hina Qayoom, Burhan Ul Haq, Shazia Sofi, Nusrat Jan, Asma Jan, Manzoor A Mir","doi":"10.1186/s12964-024-01863-9","DOIUrl":"10.1186/s12964-024-01863-9","url":null,"abstract":"<p><p>The p53 mutation is the most common genetic mutation associated with human neoplasia. TP53 missense mutations, which frequently arise early in breast cancer, are present in over thirty percent of breast tumors. In breast cancer, p53 mutations are linked to a more aggressive course of the disease and worse overall survival rates. TP53 mutations are mostly seen in triple-negative breast cancer, a very diverse kind of the disease. The majority of TP53 mutations originate in the replacement of individual amino acids within the p53 protein's core domain, giving rise to a variety of variations referred to as \"mutant p53s.\" In addition to gaining carcinogenic qualities through gain-of-function pathways, these mutants lose the typical tumor-suppressive features of p53 to variable degrees. The gain-of-function impact of stabilized mutant p53 causes tumor-specific dependency and resistance to therapy. P53 is a prospective target for cancer therapy because of its tumor-suppressive qualities and the numerous alterations that it experiences in tumors. Phenotypic abnormalities in breast cancer, notably poorly differentiated basal-like tumors are frequently linked to high-grade tumors. By comparing data from cell and animal models with clinical outcomes in breast cancer, this study investigates the molecular mechanisms that convert gene alterations into the pathogenic consequences of mutant p53's tumorigenic activity. The study delves into current and novel treatment approaches aimed at targeting p53 mutations, taking into account the similarities and differences in p53 regulatory mechanisms between mutant and wild-type forms, as well.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"484"},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402073","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":"Mutational analysis differentiating sporadic carcinomas from colitis-associated colorectal carcinomas.","authors":"Theresa Dregelies, Franziska Haumaier, William Sterlacci, Steffen Backert, Michael Vieth","doi":"10.1186/s12964-024-01856-8","DOIUrl":"10.1186/s12964-024-01856-8","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that is associated with increased risk of developing colitis-associated carcinoma (CAC). The genetic profile of CACs is fairly similar to the sporadic colorectal carcinomas (sCRCs), although showing certain differences in the timing and sequence of alterations that contribute to carcinogenesis. Also, both cancer types typically show a strong histological resemblance, which complicates the pathologists' diagnosis. Due to the different clinical consequences, it is of utmost importance to categorize the corresponding cancer type correctly.</p><p><strong>Methods: </strong>In this study, we determined the mutation profiles of 64 CACs and sCRCs in the hotspot regions of 50 cancer-associated genes and compared them to 29 controls to identify genetic gene variants that can facilitate the pathologists' diagnosis. Pearson Chi-Square or Fisher's exact tests were used for statistical analyses.</p><p><strong>Results: </strong>We found that sCRCs tend to mutate more frequently in APC and PIK3CA genes than CACs and that mainly males were affected. Our CAC cohort identified the KRAS G12D mutation as group-specific variant that was not detected in the sCRCs. When separating conventional from non-conventional CACs, it was discovered that the conventional type shows significantly more mutations for ATM.</p><p><strong>Conclusions: </strong>Taken together, our data highlights genetic differences between sCRC and CAC and enables the possibility to utilize specific gene alterations to support the pathologist's diagnosis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"483"},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402072","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":"Loss of mitochondrial Ca²⁺ response and CaMKII/ERK activation by LRRK2^R1441G mutation correlate with impaired depolarization-induced mitophagy.","authors":"Eunice Eun-Seo Chang, Huifang Liu, Zoe Yuen-Kiu Choi, Yasine Malki, Steffi Xi-Yue Zhang, Shirley Yin-Yu Pang, Michelle Hiu-Wai Kung, David B Ramsden, Shu-Leong Ho, Philip Wing-Lok Ho","doi":"10.1186/s12964-024-01844-y","DOIUrl":"10.1186/s12964-024-01844-y","url":null,"abstract":"<p><strong>Background: </strong>Stress-induced activation of ERK/Drp1 serves as a checkpoint in the segregation of damaged mitochondria for autophagic clearance (mitophagy). Elevated cytosolic calcium (Ca²⁺) activates ERK, which is pivotal to mitophagy initiation. This process is altered in Parkinson's disease (PD) with mutations in leucine-rich repeat kinase 2 (LRRK2), potentially contributing to mitochondrial dysfunction. Pathogenic LRRK2 mutation is linked to dysregulated cellular Ca²⁺ signaling but the mechanism involved remains unclear.</p><p><strong>Methods: </strong>Mitochondrial damages lead to membrane depolarization. To investigate how LRRK2 mutation impairs cellular response to mitochondrial damages, mitochondrial depolarization was induced by artificial uncoupler (FCCP) in wild-type (WT) and LRRK2^R1441G mutant knockin (KI) mouse embryonic fibroblasts (MEFs). The resultant cytosolic Ca²⁺ flux was assessed using live-cell Ca²⁺ imaging. The role of mitochondria in FCCP-induced cytosolic Ca²⁺ surge was confirmed by co-treatment with the mitochondrial sodium-calcium exchanger (NCLX) inhibitor. Cellular mitochondrial quality and function were evaluated by Seahorse™ real-time cell metabolic analysis, flow cytometry, and confocal imaging. Mitochondrial morphology was visualized using transmission electron microscopy (TEM). Activation (phosphorylation) of stress response pathways were assessed by immunoblotting.</p><p><strong>Results: </strong>Acute mitochondrial depolarization induced by FCCP resulted in an immediate cytosolic Ca²⁺ surge in WT MEFs, mediated predominantly via mitochondrial NCLX. However, such cytosolic Ca²⁺ response was abolished in LRRK2 KI MEFs. This loss of response in KI was associated with impaired activation of Ca²⁺/calmodulin-dependent kinase II (CaMKII) and MEK, the two upstream kinases of ERK. Treatment of LRRK2 inhibitor did not rescue this phenotype indicating that it was not caused by mutant LRRK2 kinase hyperactivity. KI MEFs exhibited swollen mitochondria with distorted cristae, depolarized mitochondrial membrane potential, and reduced mitochondrial Ca²⁺ store and mitochondrial calcium uniporter (MCU) expression. These mutant cells also exhibited lower cellular ATP: ADP ratio albeit higher basal respiration than WT, indicating compensation for mitochondrial dysfunction. These defects may hinder cellular stress response and signals to Drp1-mediated mitophagy, as evident by impaired mitochondrial clearance in the mutant.</p><p><strong>Conclusions: </strong>Pathogenic LRRK2^R1441G mutation abolished mitochondrial depolarization-induced Ca²⁺ response and impaired the basal mitochondrial clearance. Inherent defects from LRRK2 mutation have weakened the cellular ability to scavenge damaged mitochondria, which may further aggravate mitochondrial dysfunction and neurodegeneration in PD.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"485"},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402070","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":"Mitochondrion-based organellar therapies for central nervous system diseases.","authors":"Mengke Zhao, Jiayi Wang, Shuaiyu Zhu, Meina Wang, Chong Chen, Liang Wang, Jing Liu","doi":"10.1186/s12964-024-01843-z","DOIUrl":"10.1186/s12964-024-01843-z","url":null,"abstract":"<p><p>As most traditional drugs used to treat central nervous system (CNS) diseases have a single therapeutic target, many of them cannot treat complex diseases or diseases whose mechanism is unknown and cannot effectively reverse the root changes underlying CNS diseases. This raises the question of whether multiple functional components are involved in the complex pathological processes of CNS diseases. Organelles are the core functional units of cells, and the replacement of damaged organelles with healthy organelles allows the multitargeted and integrated modulation of cellular functions. The development of therapies that target independent functional units in the cell, specifically, organelle-based therapies, is rapidly progressing. This article comprehensively discusses the pathogenesis of mitochondrial homeostasis disorders, which involve mitochondria, one of the most important organelles in CNS diseases, and the machanisms of mitochondrion-based therapies, as well as current preclinical and clinical studies on the efficacy of therapies targeting mitochondrial to treat CNS diseases, to provide evidence for use of organelle-based treatment strategies in the future.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"487"},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402071","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":"TMEM132A regulates Wnt/β-catenin signaling through stabilizing LRP6 during mouse embryonic development.","authors":"Shin Ae Oh, Jiyeon Jeon, Su-Yeon Je, Seoyoung Kim, Joohyun Jung, Hyuk Wan Ko","doi":"10.1186/s12964-024-01855-9","DOIUrl":"10.1186/s12964-024-01855-9","url":null,"abstract":"<p><p>The Wnt/β-catenin signaling pathway is crucial for embryonic development and adult tissue homeostasis. Dysregulation of Wnt signaling is linked to various developmental anomalies and diseases, notably cancer. Although numerous regulators of the Wnt signaling pathway have been identified, their precise function during mouse embryo development remains unclear. Here, we revealed that TMEM132A is a crucial regulator of canonical Wnt/β-catenin signaling in mouse development. Mouse embryos lacking Tmem132a displayed a range of malformations, including open spina bifida, caudal truncation, syndactyly, and renal defects, similar to the phenotypes of Wnt/β-catenin mutants. Tmem132a knockdown in cultured cells suppressed canonical Wnt/β-catenin signaling. In developing mice, loss of Tmem132a also led to diminished Wnt/β-catenin signaling. Mechanistically, we showed that TMEM132A interacts with the Wnt co-receptor LRP6, thereby stabilizing it and preventing its lysosomal degradation. These findings shed light on a novel role for TMEM132A in regulating LRP6 stability and canonical Wnt/β-catenin signaling during mouse embryo development. This study provides valuable insights into the molecular intricacies of the Wnt signaling pathway. Further research may deepen our understanding of Wnt pathway regulation and offer its potential therapeutic applications.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"482"},"PeriodicalIF":8.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395481","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":"Elucidating the power of arginine restriction: taming type I interferon response in breast cancer via selective autophagy.","authors":"Apsana Lamsal, Sonja Benedikte Andersen, Ida Johansson, Marie-Catherine Drigeard Desgarnier, Camilla Wolowczyk, Nikolai Engedal, Marina Vietri, Geir Bjørkøy, Miriam S Giambelluca, Kristine Pettersen","doi":"10.1186/s12964-024-01858-6","DOIUrl":"10.1186/s12964-024-01858-6","url":null,"abstract":"<p><strong>Background: </strong>Type I interferons (IFN-I) are potent alarm factors that initiate cancer cell elimination within tumors by the immune system. This critical immune response is often suppressed in aggressive tumors, thereby facilitating cancer immune escape and unfavorable patient outcome. The mechanisms underpinning IFN-I suppression in tumors are incompletely understood. Arginase-1 (ARG1)-expressing immune cells that infiltrate tumors can restrict arginine availability by ARG1-mediated arginine degradation. We hypothesized that arginine restriction suppresses the IFN-I response in tumors.</p><p><strong>Methods: </strong>Comprehensive, unbiased open approach omics analyses, various in vitro techniques, including microscopy, qPCR, immunoblotting, knock-down experiments, and flow cytometry were employed, as well as ex vivo analysis of tumor tissue from mice. Several functional bioassays were utilized to assess metabolic functions and autophagy activity in cancer cells.</p><p><strong>Results: </strong>Arginine restriction potently induced expression of selective autophagy receptors, enhanced bulk and selective autophagy and strongly suppressed the IFN-I response in cancer cells in an autophagy-dependent manner.</p><p><strong>Conclusion: </strong>Our study proposes a mechanism for how tumor-infiltrating immune cells can promote cancer immune escape by dampening the IFN-I response. We suggest ARG1 and autophagy as putative therapeutic targets to activate the IFN-I response in tumors.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"481"},"PeriodicalIF":8.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395478","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":"Correction: SUMOylation-induced membrane localization of TRPV1 suppresses proliferation and migration in gastric cancer cells.","authors":"Yang Yang, Xiaokun Gu, Weiji Weng, Jinke Cheng, Ou Huang, Si-Jian Pan, Yong Li","doi":"10.1186/s12964-024-01864-8","DOIUrl":"https://doi.org/10.1186/s12964-024-01864-8","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"479"},"PeriodicalIF":8.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395477","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":"Correction: Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.","authors":"Jieon Hwang, Areum Park, Chinwoo Kim, Chang Gon Kim, Jaesung Kwak, Byungil Kim, Hyunjin Shin, Minhee Ku, Jaemoon Yang, Ayoung Baek, Jiwon Choi, Hocheol Lim, Kyoung Tai No, Xianghua Zhao, Uyeong Choi, Tae Il Kim, Kyu-Sung Jeong, Hyuk Lee, Sang Joon Shin","doi":"10.1186/s12964-024-01840-2","DOIUrl":"https://doi.org/10.1186/s12964-024-01840-2","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"480"},"PeriodicalIF":8.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395476","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":"Senescent cells promote breast cancer cells motility by secreting GM-CSF and bFGF that activate the JNK signaling pathway.","authors":"Nan Wang, Yan Fang, Yigong Hou, Dongmei Cheng, Emily V Dressler, Hao Wang, Juan Wang, Guanwen Wang, Yilei Li, Hong Liu, Rong Xiang, Shuang Yang, Peiqing Sun","doi":"10.1186/s12964-024-01861-x","DOIUrl":"https://doi.org/10.1186/s12964-024-01861-x","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence can be induced in mammalian tissues by multiple stimuli, including aging, oncogene activation and loss of tumor suppressor genes, and various types of stresses. While senescence is a tumor suppressing mechanism when induced within premalignant or malignant tumor cells, senescent cells can promote cancer development through increased secretion of growth factors, cytokines, chemokines, extracellular matrix, and degradative enzymes, collectively known as senescence-associated secretory phenotype (SASP). Previous studies indicated that senescent cells, through SASP factors, stimulate tumor cell invasion that is a critical step in cancer cell metastasis.</p><p><strong>Methods: </strong>In the current study, we investigated the effect of senescent cells on the motility of breast cancer cells, which is another key step in cancer cell metastasis. We analyzed the motility of breast cancer cells co-cultured with senescent cells in vitro and metastasis of the breast cancer cells co-injected with senescent cells in orthotopic xenograft models. We also delineated the signaling pathway mediating the effect of senescent cells on cancer cell motility.</p><p><strong>Results: </strong>Our results indicate that senescent cells stimulated the migration of breast cancer cells through secretion of GM-CSF and bFGF, which in turn induced activation of the JNK pathway in cancer cells. More importantly, senescent cells promoted breast cancer metastasis, with a minimum effect on the primary tumor growth, in orthotopic xenograft mouse models.</p><p><strong>Conclusions: </strong>These results have revealed an additional mechanism by which senescent cells promote tumor cell metastasis and tumor progression, and will potentially lead to identification of novel targets for cancer therapies that suppress metastasis, the major cause of cancer mortality.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"478"},"PeriodicalIF":8.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395480","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}