Journal of Cell Communication and Signaling最新文献

{"title":"Overexpressed miR-486 in bone marrow mesenchymal stem cells represses urethral fibrosis and targets Col13a1 in urethral stricture rats","authors":"Yali Xu,&nbsp;Lihong Huang,&nbsp;Zhixin Qiu,&nbsp;Jiaqi Zhang,&nbsp;Xueyi Xue,&nbsp;Junshan Lin","doi":"10.1002/ccs3.12028","DOIUrl":"10.1002/ccs3.12028","url":null,"abstract":"<p>Urethral stricture (US) is a challenging problem in urology and its pathogenesis of US is closely related to the fibrotic process. Previous evidence has indicated the downregulation of microRNA (miR)-486 in injured urethral specimens of rats. This study aimed to explore the effects of miR-486-overexpressed bone marrow mesenchymal stem cells (BMSCs) on US. BMSCs were identified by detecting their multipotency and surface antigens. Lentivirus virus expressing miR-486 was transduced into rat BMSCs to overexpress miR-486. Transforming growth factor (TGF)-β1 induced fibrotic phenotypes in urethral fibroblasts (UFs) and rat models. Western blotting showed protein levels of collagen I/III and collagen type XIII alpha 1 chain (Col13a1). Real time quantitative polymerase chain reaction was utilized for messenger RNA level evaluation. Hematoxylin-eosin, Masson's trichrome, and Von Willebrand Factor staining were conducted for histopathological analysis. Immunofluorescence staining was employed for detecting alpha smooth muscle actin (α-SMA) expression. Luciferase reporter assay verified the interaction between miR-486 and Col13a1. The results showed that miR-486-overexpressed BMSCs suppressed collagen I/III and α-SMA expression in TGF-β1-stimulated UFs. miR-486-overexpressed BMSCs alleviated urethral fibrosis, collagen deposition, and epithelial injury in the urethral tissue of US rats. miR-486 targeted and negatively regulated Col13a1 in US rats. In conclusion, overexpression of miR-486 in BMSCs targets Col13a1 and attenuates urethral fibrosis in TGF-β1-triggered UFs and US rats.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140673001","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":"LncRNA ZFAS1 promotes invasion of medullary thyroid carcinoma by enhancing EPAS1 expression via miR-214-3p/UCHL1 axis","authors":"Wenjing Chen,&nbsp;Shaoqing Wang,&nbsp;Dongmei Wei,&nbsp;Lili Zhai,&nbsp;Li Liu,&nbsp;Chunlei Pan,&nbsp;Zhongshu Han,&nbsp;Huiming Liu,&nbsp;Wei Zhong,&nbsp;Xin Jiang","doi":"10.1002/ccs3.12021","DOIUrl":"10.1002/ccs3.12021","url":null,"abstract":"<p>lncRNA ZFAS1 was identified to facilitate thyroid cancer, but its role in medullary thyroid carcinoma (MTC) remains unknown. This study aimed to unravel the potential function of this lncRNA in MTC by investigating the involvement of the lncRNA ZFAS1 in a ceRNA network that regulates MTC invasion. Proliferation, invasion, and migration of cells were evaluated using EdU staining and Transwell assays. Immunoprecipitation (IP) assays, dual-fluorescence reporter, and RNA IP assays were employed to examine the binding interaction among genes. Nude mice were used to explore the role of lncRNA ZFAS1 in MTC in vivo. ZFAS1 and EPAS1 were upregulated in MTC. Silencing ZFAS1 inhibited MTC cell proliferation and invasion under hypoxic conditions, which reduced EPAS1 protein levels. UCHL1 knockdown increased EPAS1 ubiquitination. ZFAS1 positively regulated UCHL1 expression by binding to miR-214-3p. Finally, silencing ZFAS1 significantly repressed tumor formation and metastasis in MTC. LncRNA ZFAS1 promotes invasion of MTC by upregulating EPAS1 expression via the miR-214-3p/UCHL1 axis.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140709733","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":"Scutellarin alleviates microglia-mediated neuroinflammation and apoptosis after ischemic stroke through the PI3K/AKT/GSK3β signaling pathway","authors":"Zhaoda Duan,&nbsp;Haolun Chen,&nbsp;Wei Miao,&nbsp;Jing He,&nbsp;Dongyao Xu,&nbsp;Zhi Qi,&nbsp;Li Yang,&nbsp;Wenji Jia,&nbsp;Chunyun Wu","doi":"10.1002/ccs3.12023","DOIUrl":"10.1002/ccs3.12023","url":null,"abstract":"<p>Microglia are resident immune cells in the central nervous system that are rapidly activated to mediate neuroinflammation and apoptosis, thereby aggravating brain tissue damage after ischemic stroke (IS). Although scutellarin has a specific therapeutic effect on IS, the potential target mechanism of its treatment has not been fully elucidated. In this study, we explored the potential mechanism of scutellarin in treating IS using network pharmacology. Lipopolysaccharide (LPS) was used to induce an in vitro BV-2 microglial cell model, while middle cerebral artery occlusion (MCAO) was used to induce an in vivo animal model. Our findings indicated that scutellarin promoted the recovery of cerebral blood flow in MCAO rats at 3 days, significantly different from that in the MCAO group. Western blotting and immunofluorescence revealed that scutellarin treatment of BV-2 microglial cells resulted in a significant reduction in the protein expression levels and incidence of cells immunopositive for p-NF-<i>κ</i>B, TNF-<i>α</i>, IL-1<i>β</i>, Bax, and C-caspase-3. In contrast, the expression levels of p-PI3K, p-AKT, p-GSK3<i>β</i>, and Bcl-2 were further increased, significantly different from those in the LPS group. The PI3K inhibitor LY294002 had similar effects to scutellarin by inhibiting neuroinflammation and apoptosis in activated microglia. The results of the PI3K/AKT/GSK3<i>β</i> signaling pathway and NF-<i>κ</i>B pathway in vivo in MCAO models induced microglia at 3 days were consistent with those obtained from in vitro cells. These findings indicate that scutellarin plays a neuroprotective role by reducing microglial neuroinflammation and apoptosis mediated by the activated PI3K/AKT/GSK3<i>β</i>/NF-<i>κ</i>B signaling pathway.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140711708","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":"Matricellular proteins: Potential biomarkers in head and neck cancer","authors":"Yunsheng Wang,&nbsp;Xudong Liu,&nbsp;Xingyue Wang,&nbsp;Jiyong Lu,&nbsp;Youxin Tian,&nbsp;Qinjiang Liu,&nbsp;Jincai Xue","doi":"10.1002/ccs3.12027","DOIUrl":"10.1002/ccs3.12027","url":null,"abstract":"<p>The extracellular matrix (ECM) is a complex network of diverse multidomain macromolecules, including collagen, proteoglycans, and fibronectin, that significantly contribute to the mechanical properties of tissues. Matricellular proteins (MCPs), as a family of non-structural proteins, play a crucial role in regulating various ECM functions. They exert their biological effects by interacting with matrix proteins, cell surface receptors, cytokines, and proteases. These interactions govern essential cellular processes such as differentiation, proliferation, adhesion, migration as well as multiple signal transduction pathways. Consequently, MCPs are pivotal in maintaining tissue homeostasis while orchestrating intricate molecular mechanisms within the ECM framework. The expression level of MCPs in adult steady-state tissues is significantly low; however, under pathological conditions such as inflammation and cancer, there is a substantial increase in their expression. In recent years, an increasing number of studies have focused on elucidating the role and significance of MCPs in the development and progression of head and neck cancer (HNC). During HNC progression, there is a remarkable upregulation in MCP expression. Through their distinctive structure and function, they actively promote tumor growth, invasion, epithelial-mesenchymal transition, and lymphatic metastasis of HNC cells. Moreover, by binding to integrins and modulating various signaling pathways, they effectively execute their biological functions. Furthermore, MCPs also hold potential as prognostic indicators. Although the star proteins of various MCPs have been extensively investigated, there remains a plethora of MCP family members that necessitate further scrutiny. This article comprehensively examines the functionalities of each MCP and highlights the research advancements in the context of HNC, with an aim to identify novel biomarkers for HNC and propose promising avenues for future investigations.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140724888","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":"Adipocyte enhancer binding protein 1 knockdown alleviates osteoarthritis through inhibiting NF-κB signaling pathway-mediated inflammation and extracellular matrix degradation","authors":"Le Cao,&nbsp;Weilu Gao,&nbsp;Haitao Yang,&nbsp;Ran Zeng,&nbsp;Zongsheng Yin","doi":"10.1002/ccs3.12022","DOIUrl":"10.1002/ccs3.12022","url":null,"abstract":"<p>Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients (<i>n</i> = 20) compared to their normal controls (<i>n</i> = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1β treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1β-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140214795","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":"LncRNA HOTTIP promotes LPS-induced lung epithelial cell injury by recruiting DNMT1 to epigenetically regulate SP-C","authors":"Shuang Li,&nbsp;Shuangjia Li,&nbsp;Zhanqun Gao,&nbsp;Yang Liu","doi":"10.1002/ccs3.12020","DOIUrl":"https://doi.org/10.1002/ccs3.12020","url":null,"abstract":"<p>The objective of this study was to elucidate the involvement of the long noncoding RNA (lncRNA) HOTTIP in acute lung injury and understand the underlying mechanisms. Relevant expression of mRNAs and proteins were assessed by qRT-PCR and western blot assays. Cell viability was determined by employing the CCK-8 assay, and apoptosis was quantified through TUNEL staining. The concentration of inflammatory factors was measured by ELISA. The degree of DNA methylation was quantified through MSP assay. The interaction between HOTTIP and DNA methyltransferase 1 (DNMT1) was examined by RIP assay. LPS upregulated HOTTIP, whereas downregulated SP-C level in AEC II cells. HOTTIP knockdown inhibited LPS-induced apoptosis and the secretion of inflammatory cytokines (TNF-<i>α</i>, IL-1<i>β</i> and IL-6) in AEC II cells. Mechanistically, HOTTIP recruited DNMT1 to the SP-C promoter, thereby facilitating DNA methylation of SP-C and suppressing its expression. Additionally, inhibitory of SP-C reversed the effects of HOTTIP or DNMT1 knockdown on apoptosis and inflammation in AEC II cells induced by LPS. HOTTIP recruited DNMT1 to epigenetically inhibit SP-C expression, leading to the promotion of lung epithelial cell injury caused by LPS, suggesting that targeting HOTTIP may be an effective strategy for the therapy of lung epithelial cell injury.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140104548","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":"Role for CCN1 in lysophosphatidic acid response in PC-3 human prostate cancer cells","authors":"Pravita Balijepalli,&nbsp;Brianna K. Knode,&nbsp;Samuel A. Nahulu,&nbsp;Emily L. Abrahamson,&nbsp;Mary P. Nivison,&nbsp;Kathryn E. Meier","doi":"10.1002/ccs3.12019","DOIUrl":"https://doi.org/10.1002/ccs3.12019","url":null,"abstract":"<p>Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive phospholipids that act as mitogens in various cancers. Both LPA and S1P activate G-protein coupled receptors (GPCRs). We examined the role of CCN1/CYR61, an inducible matricellular protein, in LPA-induced signal transduction in PC-3 human prostate cancer cells. We found that both LPA and S1P induced expression of CCN1 and CCN2 within 2–4 h. CCN1 was induced by 18:1-LPA, but not by 18:0-, 18:2-, or 18:3-LPAs. A free fatty acid receptor-4 agonist inhibited LPA-induced CCN1 induction. CCN1 appeared in the ECM within 2 h after LPA addition. LPA caused biphasic activation of Erk MAPK, with an initial peak at 10–20 min followed by a later phase after 6 h. LPA increased adhesion of PC-3 cells to culture substrates (standard culture plates, fibronectin, or extracellular matrix) at 2 h, an intermediate event between early and late LPA signals. Knockdown of CCN1 suppressed LPA-induced adhesion to ECM or fibronectin. ECM from CCN1 knockdown cells was a poor substrate for adhesion, as compared to ECM from control cells. These results suggest that CCN1 contributes to LPA responses in the tumor microenvironment. The LPA-CCN1 axis holds promise for the development of novel therapeutic strategies in cancer.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140104540","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":"Lactate drives CD38 signaling to promote Epithelial-Mesenchymal Transition through Snail induction in non-small cell lung cancer cells","authors":"Yating Lu,&nbsp;Yang Yang,&nbsp;Tao Chang,&nbsp;Qiyun Jiang,&nbsp;Chenfeng Yang,&nbsp;Chunzhe Fu,&nbsp;Huijun Wei,&nbsp;Yuanpeng He,&nbsp;Zhihao Wu","doi":"10.1002/ccs3.12018","DOIUrl":"10.1002/ccs3.12018","url":null,"abstract":"<p>CD38 is the main NADase in mammalian cells. It regulates the homeostasis of nicotinamide adenine dinucleotide (NAD+) and extracellular nucleotides. Its function plays an important role in infection and aging. However, its potential functions in tumor cells have not been fully elucidated. In the present study, we demonstrated that lactate, which is derived from tumor metabolism remodeling, upregulates the expression of CD38 through OXPHOS-driven Hippo-TAZ pathway. The highly expressed CD38 converts NAD + to adenosine through the CD203a/CD73 complex and adenosine binds and activates its receptor A2AR, inducing the expression of Snail and promoting the invasion and metastasis of lung cancer cells. This finding elucidates a new perspective on the interplay between NAD + metabolism and glycolysis in tumor development.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838153","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":"IncRNA AC004943.2 regulates miR-135a-5p and PTK2/P13K axis to promote laryngeal squamous cell carcinoma progression","authors":"Xiaowen Zhu,&nbsp;Wenming Dong,&nbsp;Meijia Zhang","doi":"10.1002/ccs3.12016","DOIUrl":"10.1002/ccs3.12016","url":null,"abstract":"<p>Long noncoding RNAs (lncRNAs) are involved in regulatory processes in laryngeal squamous cell carcinoma (LSCC) at posttranscriptional epigenetic modification level. Yet, the function and underlying mechanism behind lncRNA AC004943.2 in LSCC is still obscure. Therefore, the potential role of AC004943.2 in LSCC progression was investigated. The expression of gene or protein was tested by real-time quantitative polymerase chain reaction and western blot. MTT, colony formation, wound healing, and transwell experiments were applied to detect LSCC cell viability, proliferation, migration and invasion, respectively. The interaction among AC004943.2, miR-135a-5p, and protein tyrosine kinase 2 (PTK2) were analyzed by bioinformatics prediction and luciferase assay. AC004943.2 was highly expressed in LSCC cells compared with normal human bronchial epithelial cells, while miR-135a-5p was lowly expressed. AC004943.2 knockdown or miR-135a-5p overexpression inhibited LSCC cell viability, proliferation, migration and invasion. Mechanistically, AC004943.2 increased PTK2 expression in LSCC cells by sponging miR-135a-5p. Furthermore, miR-135a-5p knockdown inverted the inhibitory effect of AC004943.2 silencing on LSCC cell malignant behaviors. MiR-135a-5p upregulation attenuated the PTK2/PI3K pathway to inhibit progression of LSCC. AC004943.2 facilitated the cancerous phenotypes of LSCC cells by activating the PTK2/PI3K pathway through targeting miR-135a-5p, which furnished a therapeutic candidate for LSCC treatment.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139789559","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":"JAK3/STAT5 signaling-triggered upregulation of PIK3CD contributes to gastric carcinoma development","authors":"Qingqing Hu,&nbsp;Ning Dou,&nbsp;Qiong Wu,&nbsp;Yong Gao,&nbsp;Yandong Li,&nbsp;Jingde Chen","doi":"10.1002/ccs3.12017","DOIUrl":"10.1002/ccs3.12017","url":null,"abstract":"<p>Gastric cancer (GC) is one of the most common solid cancers with high incidence and mortality worldwide. Chronic gastritis and consequent inflammatory microenvironment is known as a major cause leading to gastric carcinogenesis. Here we report that PIK3CD that encodes p110δ, a catalytic subunit of the class IA PI3Ks, is overexpressed and tumorigenic in GC and associated with tumor inflammatory microenvironment. By investigating the data from TCGA database and our immunohistochemical staining and quantitative real-time PCR results from clinical samples, we found PIK3CD exhibits higher expression level in GC tissues compared with adjacent non-tumorous stomach tissues. Genetic silencing of PIK3CD in GC cells retards proliferation and migration in vitro and tumorigenicity and metastasis in vivo. In contrast, enhanced expression of PIK3CD promotes these phenotypes in vitro. Furthermore, pharmacological inhibition of PIK3CD could reduce GC cell viability and colony formation capacities. More importantly, we reveal a relevant mechanism that PIK3CD, but not PIK3CA and PIK3CB, is transcriptionally regulated by the pro-inflammatory IL2/JAK3/STAT5 axis and tumor-infiltrating immune cells such as lymphocytes. These observations may setup a new crosstalk between tumor inflammatory microenvironment, IL2/JAK3/STAT5 signaling and PI3K/AKT signaling. Targeting PIK3CD may be a promising therapy strategy for GC.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"18 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139795808","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}