Journal of Cell Communication and Signaling最新文献

{"title":"Role of TLRs in EGFR-mediated IL-8 secretion by enteroaggregative Escherichia coli-infected cultured human intestinal epithelial cells","authors":"Archana Joon,&nbsp;Shipra Chandel,&nbsp;Sujata Ghosh","doi":"10.1007/s12079-023-00776-5","DOIUrl":"10.1007/s12079-023-00776-5","url":null,"abstract":"<div>\u0000 \u0000 <p>Enteroaggregative <i>Escherichia coli</i> (EAEC) is an emerging enteric pathogen associated with persistent diarrhea in travelers, immunocompromised patients and children worldwide. However, the pathogenesis of this organism is yet to be established. In this study, the role of Toll-like receptors (TLRs) was evaluated in epidermal growth factor receptor (EGFR)-mediated IL-8 secretion by EAEC-infected human small intestinal and colonic epithelial cells (INT-407 and HCT-15, respectively). We observed that EAEC-induced upregulation of TLR2, TLR4 and TLR5 transcripts in both types of cells, and the maximum level of these transcripts was seen in cells infected with EAEC-T8 (an invasive clinical isolate). All these TLRs made a significant contribution to the EAEC-T8-mediated EGFR activation in these cells. Furthermore, these TLRs were found to be associated with activation of the downstream effectors (ERK-1/2, PI3 kinase and Akt) and transcription factors (NF-κB, c-Jun, c-Fos and STAT-3) of EGFR-mediated signal transduction pathways. Moreover, the involvement of these TLRs was also noted in IL-8 secretion by both EAEC-T8-infected cell types. Our findings suggest that EAEC-induced upregulation of TLR2, TLR4 and TLR5 is important for the IL-8 response via EGFR-mediated signal transduction pathways in these cells.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 4","pages":"1355-1370"},"PeriodicalIF":3.6,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10713919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9673293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of Yap attenuates TAA-induced hepatic fibrosis by interaction with hedgehog signals","authors":"Ye Zhao,&nbsp;Huiling Wang,&nbsp;Tianhua He,&nbsp;Bo Ma,&nbsp;Guoguang Chen,&nbsp;Chimeng Tzeng","doi":"10.1007/s12079-023-00775-6","DOIUrl":"10.1007/s12079-023-00775-6","url":null,"abstract":"<div>\u0000 \u0000 <p>Liver fibrosis is an aberrant wound healing response to tissue injury characterized by excessive extracellular matrix deposition and loss of normal liver architecture. Hepatic stellate cells (HSCs) activation is regards to be the major process in liver fibrogenesis which is dynamic and reversible. Both Hippo signaling core factor Yap and Hedgehog (Hh) signaling promote HSCs transdifferentiation thereby regulating the repair process of liver injury. However, the molecular function of YAP and the regulation between Yap and Hh during fibrogenesis remain uncertain. In this study, the essential roles of Yap in liver fibrosis were investigated. Yap was detected to be increased in liver fibrotic tissue by the thioacetamide (TAA)-induced zebrafish embryonic and adult models. Inhibition of Yap by both embryonic morpholino interference and adult's inhibitor treatment was proved to alleviate TAA-induced liver lesions by and histology and gene expression examination. Transcriptomic analysis and gene expression detection showed that Yap and Hh signaling pathway have a cross talking upon TAA-induced liver fibrosis. In addition, TAA induction promoted the nuclear colocalization of YAP and Hh signaling factor GLI2α. This study demonstrates that Yap and Hh play synergistic protective roles in liver fibrotic response and provides new theoretical insight concerning the mechanisms of fibrosis progression.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 4","pages":"1335-1354"},"PeriodicalIF":3.6,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10713942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of the long non-coding RNA NEAT1 in gynecologic cancers","authors":"Maryam Farzaneh,&nbsp;Mahrokh Abouali Gale Dari,&nbsp;Amir Anbiyaiee,&nbsp;Sajad Najafi,&nbsp;Dian Dayer,&nbsp;Abdolah Mousavi Salehi,&nbsp;Mona Keivan,&nbsp;Mehri Ghafourian,&nbsp;Shahab Uddin,&nbsp;Shirin Azizidoost","doi":"10.1007/s12079-023-00746-x","DOIUrl":"10.1007/s12079-023-00746-x","url":null,"abstract":"<div>\u0000 \u0000 <p>Gynecologic cancers are a worldwide problem among women. Recently, molecular targeted therapy opened up an avenue for cancer diagnosis and treatment. Long non-coding RNAs (lncRNAs) are RNA molecules (&gt; 200 nt) that are not translated into protein, and interact with DNA, RNA, and proteins. LncRNAs were found to play pivotal roles in cancer tumorigenesis and progression. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a lncRNA that mediates cell proliferation, migration, and EMT in gynecologic cancers by targeting several miRNAs/mRNA axes. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of breast, ovarian, cervical, and endometrial cancers. In this narrative review, we summarized various NEAT1-related signaling pathways that are critical in gynecologic cancers.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"531-547"},"PeriodicalIF":4.1,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9972980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antitumor effects of WNT5A against hematological malignancies","authors":"Maura Lima Pereira Bueno,&nbsp;Sara Teresinha Olalla Saad,&nbsp;Fernanda Marconi Roversi","doi":"10.1007/s12079-023-00773-8","DOIUrl":"10.1007/s12079-023-00773-8","url":null,"abstract":"<div>\u0000 \u0000 <p>The bone marrow (BM) microenvironment (niche) is abnormally altered in acute myeloid leukemia (AML), leading to deficient secretion of proteins, soluble factors, and cytokines by mesenchymal stromal cells (MSC) that modifies the crosstalk between MSC and hematopoietic cells. We focused on a WNT gene/protein family member, WNT5A, which is downregulated in leukemia and correlated with disease progression and poor prognosis. We demonstrated that WNT5A protein upregulated the WNT non-canonical pathway only in leukemic cells, without modulating normal cell behavior. We also introduced a novel WNT5A-mimicking compound, Foxy-5. Our results showed reduction of crucial biological functions that are upregulated in leukemia cells, including ROS generation, cell proliferation, and autophagy, as well as G0/G1 cell cycle arrest. Additionally, Foxy-5 induced early-stage macrophage cell differentiation, a crucial process during leukemia development. At a molecular level, Foxy-5 led to the downregulation of two overexpressed leukemia pathways, PI3K and MAPK, which resulted in a disarrangement of actin polymerization with consequent impairment of CXCL12-induced chemotaxis. Notably, in a novel tri-dimensional bone marrow-mimicking model, Foxy-5 led to reduced leukemia cell growth and similar results were observed in a xenograft in vivo model. Overall, our findings highlight the pivotal role of WNT5A in leukemia and demonstrate that Foxy-5 acts as a specific antineoplastic agent in leukemia, counterbalancing several leukemic oncogenic processes related to the crosstalk in the bone marrow niche, and represents a promising therapeutic option for AML.\u0000</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 4","pages":"1487-1499"},"PeriodicalIF":3.6,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10713930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Long non-coding RNA TP73-AS1 promotes TFAP2B-mediated proliferation, metastasis and invasion in retinoblastoma via decoying of miRNA-874-3p","authors":"Lina Wang,&nbsp;Chaokui Wang,&nbsp;Tong Wu,&nbsp;Fengyuan Sun","doi":"10.1007/s12079-023-00774-7","DOIUrl":"10.1007/s12079-023-00774-7","url":null,"abstract":"<p><b>Retraction Note: Journal of Cell Communication and Signaling (2020) 14:193–205</b></p><p>https://doi.org/10.1007/s12079-020-00550-x</p><p>The Editor-in-Chief has retracted this article. After publication, concerns were raised regarding high similarity between Fig. 5g (HXO-RB44 pcDNA-TP73-AS1 + NC mimic) in this article and Fig. 4g (HCT116 group 2) in Wang et al. (<span>2019</span>). The authors have been unable to provide raw data to address these concerns. The Editor-in-Chief therefore no longer has confidence in the presented data.</p><p>Fengyuan Sun does not agree to this retraction. Lina Wang, Chaokui Wang and Tong Wu have not responded to any correspondence from the editor or publisher about this retraction.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"1121"},"PeriodicalIF":4.1,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409937/pdf/12079_2023_Article_774.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10024270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCNs and other extracellular matrix proteins: an introduction to the special issue","authors":"Ralf Weiskirchen","doi":"10.1007/s12079-023-00770-x","DOIUrl":"10.1007/s12079-023-00770-x","url":null,"abstract":"&lt;p&gt;The extracellular matrix (ECM) is a specialized, highly organized and dynamic three-dimensional network composed of a complex mixture of proteins and other molecules forming the physical scaffolding of a cell and determining the tissue architecture of organs (Rais et al., &lt;span&gt;2023&lt;/span&gt;). It is of fundamental importance in cell growth, cell migration, and cellular communication. It is further a reservoir for growth factors and an anchor for cell-matrix, cell adhesion, and signaling receptors (Kyriakopoulou et al. &lt;span&gt;2023&lt;/span&gt;). Altered composition or dysregulated ECM remodeling can result in a wide range of diseases that include tissue stiffening, connective tissue disorders, muscular dystrophy, fibrosis, and cancer. Therefore, there is hope that increasing knowledge on the mechanisms that regulate ECM composition will lead to improved diagnostics and novel strategies for repair and regeneration of affected tissues (Keane et al. &lt;span&gt;2018&lt;/span&gt;). In particular, the six centralized coordinating network (CCN1-CCN6) factors represent general hubs that operate through diverse signaling pathways, thereby impacting a wide array of biological properties in tissue homeostasis and malignancy (Yeger and Perbal &lt;span&gt;2021&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;This Special Issue of &lt;i&gt;Journal of Cell Communication and Signaling&lt;/i&gt; (JCCS) entitled “&lt;i&gt;CCNs and other extracellular matrix proteins&lt;/i&gt;” contains a comprehensive editorial, 7 reviews, and 4 original research articles reporting novel concepts and major advances in our understanding of basic and clinical aspects on CCN biology. The collection of these articles demonstrates the eminent progress made in the CCN field during the last years and supports the hope that this knowledge will help establishing novel therapies for various pathologies associated with imbalance or de-regulation of CCN proteins and pathways modulated by this multifaceted protein family.&lt;/p&gt;&lt;p&gt;The first contribution in this Special Issue is a profound Editorial by Perbal et al. (&lt;span&gt;2023&lt;/span&gt;) in which exciting basic principles, concepts, new views and considerations on the CCN family of protein are discussed. The article highlights important theoretical and conceptual considerations on how CCN family members can coordinate different signaling pathways. Strikingly, individual CCN members are functional “bipartite-acting” mediators, with members acting negatively and/or positively on cell proliferation and differentiation. As such, it is critical that expression of CCN members is under strict time- and tissue-specific regulation. The article further provides an extensive reference work for the CCN interactome. Importantly, the four structural modules of CCNs (i.e., insulin-like growth factor binding domain, von Willebrand factor-C domain, thrombospondin type 1 repeat domain, and carboxy-terminal cysteine knot domain) can interact with a high number of distinct ligands. Thus, it is estimated that different combinations of possible bindin","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 2","pages":"229-232"},"PeriodicalIF":4.1,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10153352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tripartite motif–containing 9 promoted proliferation and migration of bladder cancer cells through CEACAM6-Smad2/3 axis","authors":"Zhao-Cun Zhang,&nbsp;Hai-Feng Zhao,&nbsp;Zhuang Sun,&nbsp;Yi Li,&nbsp;Ming-Lei Zhong,&nbsp;Bao-Hai Wang,&nbsp;Xian-Zhou Jiang","doi":"10.1007/s12079-023-00766-7","DOIUrl":"10.1007/s12079-023-00766-7","url":null,"abstract":"<div>\u0000 \u0000 <p>Studies have shown that tripartite motif–containing (TRIM) family proteins function as E3 ubiquitin ligases and play essential roles in cancer biology. In the present study, we validated a contribution of TRIM9 to bladder cancer progression. 296 patients derived from The Cancer Genome Atlas (TCGA) database and 22 clinical specimens were included, in which accumulated TRIM9 correlated with the poor prognosis and higher relapse in bladder patients. In vitro, TRIM9 promoted bladder cancer cells Biu-87 and T24 cell proliferation and migration. Meanwhile, overexpression of TRIM9 reduced the chemosensitivity in Biu-87 and T24 to mitomycin C (MMC) and gemcitabine (GEM). As an underlying mechanism, we found that TRIM9 stimulated carcinoembryonic antigen 6 (CEACAM6) upregulation, which further facilitated Smad2/3-matrix metalloproteinase 2 (MMP2) signaling activation both in vitro and in vivo. Those results indicated that TRIM9 facilitated bladder cancer development and chemoresistance by CEACAM6-Smad2/3 axis. TRIM9 and its associated molecules could be a potential diagnostic indicator and therapeutic target in bladder cancer.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 4","pages":"1323-1333"},"PeriodicalIF":3.6,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10713968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9540310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCN1 is predominantly elevated in human skin dermis by solar-simulated ultraviolet irradiation and accumulated in dermal extracellular matrix","authors":"Zhaoping Qin,&nbsp;Tianyuan He,&nbsp;Chunfang Guo,&nbsp;Jun Young Kim,&nbsp;Taihao Quan","doi":"10.1007/s12079-023-00767-6","DOIUrl":"10.1007/s12079-023-00767-6","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin primarily comprises a collagen-rich extracellular matrix (ECM) that provides structural and functional support to the skin. Aging causes progressive loss and fragmentation of dermal collagen fibrils, leading to thin and weakened skin (Dermal aging). We previously reported that CCN1 is elevated in naturally aged human skin, photoaged human skin, and acute UV-irradiated human skin dermal fibroblasts in vivo. Elevated CCN1 alters the expression of numerous secreted proteins that have deleterious effects on the dermal microenvironment, impairing the structural integrity and function of the skin. Here we show that CCN1 is predominantly elevated in the human skin dermis by UV irradiation and accumulated in the dermal extracellular matrix. Laser capture microdissection indicated that CCN1 is predominantly induced in the dermis, not in the epidermis, by acute UV irradiation in human skin in vivo. Interestingly, while UV-induced CCN1 in the dermal fibroblasts and in the medium is transient, secreted CCN1 accumulates in the ECM. We explored the functionality of the matrix-bound CCN1 by culturing dermal fibroblasts on an acellular matrix plate that was enriched with a high concentration of CCN1. We observed that matrix-bound CCN1 activates integrin outside-in signaling resulting in the activation of FAK and its downstream target paxillin and ERK, as well as elevated MMP-1 and inhibition of collagen, in human dermal fibroblasts. These data suggest that accumulation of CCN1 in the dermal ECM is expected to progressively promote the aging of the dermis and thereby negatively impact the function of the dermis.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 2","pages":"287-296"},"PeriodicalIF":4.1,"publicationDate":"2023-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326203/pdf/12079_2023_Article_767.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent progress on the role of cellular communication network factors (CCN) 3, 4 and 6 in regulating adiposity, liver fibrosis and pancreatic islets","authors":"Viktoria Xega,&nbsp;Tara Alami,&nbsp;Jun-Li Liu","doi":"10.1007/s12079-023-00765-8","DOIUrl":"10.1007/s12079-023-00765-8","url":null,"abstract":"<div>\u0000 \u0000 <p>CCN/WISP (cellular communication network factors, or Wnt-inducted secreted proteins) family of proteins consists of six extracellular matrix (ECM)-associated proteins that regulate development, cell adhesion and proliferation, ECM remodeling, inflammation, and tumorigenesis. In the last two decades, metabolic regulation by these matricellular proteins has been studied extensively, several excellent reviews have covered the roles of CCN1, -2 and − 5. In this brief review, we will focus on those lesser-known members and more recent discoveries, together with other recent articles presenting a more complete picture of the current state of knowledge. We have found that CCN2, -4, and − 5 promote pancreatic islet function, while CCN3 plays a unique and negative role. CCN3 and − 4 are pro-adiposity leading to insulin resistance, but CCN5 and − 6 are anti-adiposity. While CCN2 and − 4 promote tissue fibrosis and inflammation, all other four members are clearly anti-fibrotic. As for cellular signaling, they are known to interact with integrins, other cell membrane proteins and ECM thereby regulate Akt/protein kinase B, myocardin-related transcription factor (MRTF), and focal adhesion kinase. Yet, a cohesive mechanism of action to comprehensively explain those major functions is still lacking.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 2","pages":"297-306"},"PeriodicalIF":4.1,"publicationDate":"2023-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326175/pdf/12079_2023_Article_765.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9795081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural insights into regulation of CCN protein activities and functions","authors":"Vivi Talstad Monsen,&nbsp;Håvard Attramadal","doi":"10.1007/s12079-023-00768-5","DOIUrl":"10.1007/s12079-023-00768-5","url":null,"abstract":"<div>\u0000 \u0000 <p>CCN proteins play important functions during development, in repair mechanisms following tissue injury, as well as in pathophysiologic mechanisms of metastasis of cancer. CCNs are secreted proteins that have a multimodular structure and are categorized as matricellular proteins. Although the prevailing view is that CCN proteins regulate biologic processes by interacting with a wide array of other proteins in the microenvironment of the extracellular matrix, the molecular mechanisms of action of CCN proteins are still poorly understood. Not dissuading the current view, however, the recent appreciation that these proteins are signaling proteins in their own right and may even be considered preproproteins controlled by endopeptidases to release a C-terminal bioactive peptide has opened new avenues of research. Also, the recent resolution of the crystal structure of two of the domains of CCN3 have provided new knowledge with implications for the entire CCN family. These resolved structures in combination with structural predictions based upon the AlphaFold artificial intelligence tool provide means to shed new light on CCN functions in context of the notable literature in the field. CCN proteins have emerged as important therapeutic targets in several disease conditions, and clinical trials are currently ongoing. Thus, a review that critically discusses structure - function relationship of CCN proteins, in particular as it relates to interactions with other proteins in the extracellular milieu and on the cell surface, as well as to cell signaling activities of these proteins, is very timely.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 2","pages":"371-390"},"PeriodicalIF":4.1,"publicationDate":"2023-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}