Xiaoming Zhao, Shaobo Wu, Xiaochen Su, Jun Gao, Lian Qu, Yilei Zhang, Yingang Zhang
{"title":"Bidirectional Regulatory Mechanisms of Disulfidptosis Govern Precision Targeting in Degenerative Bone Diseases and Osteosarcoma","authors":"Xiaoming Zhao, Shaobo Wu, Xiaochen Su, Jun Gao, Lian Qu, Yilei Zhang, Yingang Zhang","doi":"10.1002/jcp.70100","DOIUrl":"10.1002/jcp.70100","url":null,"abstract":"<div>\u0000 \u0000 <p>Disulfidptosis is a newly identified form of programmed cell death closely associated with cystine metabolism abnormalities and cytoskeletal damage. Orthopedic diseases, such as degenerative conditions including intervertebral disc degeneration, osteoporosis, osteoarthritis, and malignant bone tumors like osteosarcoma, all involve imbalances in the immunometabolic microenvironment. The triggering conditions for disulfidptosis, such as high expression of SLC7A11 and glucose deprivation, are highly correlated with the pathaological features of orthopedic diseases and associated immune dysregulation. However, there is currently a lack of systematic understanding regarding the regulatory networks, molecular markers, and intervention strategies of disulfidptosis in orthopedic diseases, and the specific mechanisms by which it contributes to disease onset and progression remain unclear. This review systematically summarizes the bidirectional immunometabolic regulatory molecular mechanisms, pathological associations, and potential therapeutic strategies of disulfidptosis in orthopedic degenerative diseases and bone tumors. By analyzing the immunometabolic regulatory networks of key molecules such as SLC7A11, TXNRD1, and RPN1, we propose immune-aware precision strategies combining disulfidptosis-targeted metabolic intervention with checkpoint blockade immunotherapy. This review fills the gap in the research of disulfidptosis in orthopedic diseases, providing new insights for a deeper understanding of the molecular mechanisms underlying these conditions, while establishing a theoretical framework for developing precise therapeutic strategies based on the regulation of disulfidptosis.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hana Lee, Jang-Mi Bae, Seung-Phil Shin, Woong Kim, Won-Jin Kim, Hyeon-Gu Kang, Da-Bin Choi, Yu-Seon Lee, Seok-Jun Kim
{"title":"CD200 Promotes Gastric Cancer Progression and Metastasis by Inducing the β-catenin Signaling Pathway","authors":"Hana Lee, Jang-Mi Bae, Seung-Phil Shin, Woong Kim, Won-Jin Kim, Hyeon-Gu Kang, Da-Bin Choi, Yu-Seon Lee, Seok-Jun Kim","doi":"10.1002/jcp.70101","DOIUrl":"10.1002/jcp.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastric cancer is the fifth most common malignancy and the fourth leading cause of cancer-related mortalities worldwide. Understanding the mechanisms driving tumor growth and metastasis in gastric cancer is essential for the development of effective therapeutic strategies. In this regard, it is well-established that CD200, a glycoprotein that binds to the CD200 receptor, has notable immunosuppressive effects. The extracellular domain of CD200 is secreted into the tumor microenvironment (TME), wherein it promotes cancer progression. However, although CD200 is highly expressed in several types of cancers, the details of its intracellular roles in tumor progression remain poorly understood. In this study, we investigated the biological function and mechanism of action of CD200 in gastric cancer. Public datasets from GSE and TCGA revealed that CD200 is overexpressed in gastric cancer and that its expression is correlated with cancer stage and metastasis. Functionally, we found that CD200 enhances cell proliferation, migration, and invasion, and also promotes the expression of epithelial-mesenchymal transition (EMT)-related genes. Mechanistically, CD200 was demonstrated activate the WNT/β-catenin signaling pathway by inducing β-catenin activation. Notably, we established that the cytoplasmic domain of CD200 binds directly to β-catenin, thereby facilitating its nuclear translocation. The CD200/β-catenin/TCF4 complex subsequently promotes the transcription of β-catenin target and EMT-related genes. Collectively, our findings in this study revealed that the cytoplasmic domain of CD200 interacts with β-catenin, thereby promoting the transcriptional activation of β-catenin target genes and inducing tumor growth and metastasis in gastric cancer. These findings accordingly indicate that CD200 may serve as a potential therapeutic target for the treatment of gastric cancer.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biplab Chaterjee, Gal Gozlan, Chen Abramovitch-Dahan, Anton Davydok, Anat Reiner-Benaim, Johannes Krug, Katharina Jähn-Rickert, Björn Busse, Noam Levaot
{"title":"The Role of GPR39 in Regulating Osteoblast Function, Bone Matrix Quality, and Gender-Specific Bone Homeostasis","authors":"Biplab Chaterjee, Gal Gozlan, Chen Abramovitch-Dahan, Anton Davydok, Anat Reiner-Benaim, Johannes Krug, Katharina Jähn-Rickert, Björn Busse, Noam Levaot","doi":"10.1002/jcp.70095","DOIUrl":"https://doi.org/10.1002/jcp.70095","url":null,"abstract":"<p>GPR39, a zinc-sensing receptor, is essential for bone homeostasis in male mice through regulation of osteoblast function and matrix composition. This study examined the effects of GPR39 deficiency in female mice using both global and osteoblast lineage-specific GPR39 knockout models (<i>Gpr39</i><sup><i>Ob</i>−<i>/Ob</i>−</sup>). In vivo, GPR39-deficient female mice exhibited reduced bone mass, increased mineralization rates, and significantly lower and more variable serum levels of pro-collagen type I N-propeptide (PINP), indicating impaired collagen synthesis and matrix remodeling. OVX models further demonstrated that GPR39 deficiency exacerbates estrogen-deficiency-induced bone loss, highlighting its protective role in postmenopausal-like states. Osteoblast lineage-specific GPR39 deletion replicated the skeletal abnormalities observed in global knockouts, revealing that GPR39 activity in the osteoblast lineage is indispensable for proper collagen deposition and mineralization. Western blot analysis of <i>Gpr39</i><sup><i>Ob</i>−<i>/Ob</i>−</sup> osteoblasts confirmed reduced extracellular collagen levels, while quantitative mRNA analysis of Col1a2 revealed zinc signaling through GPR39 as a key regulator of collagen production. Zinc-induced Col1a2 expression, dependent on GPR39 and mediated via Gα<sub>q</sub> signaling, was abolished in GPR39-deficient osteoblasts. These findings provide insights into how zinc signaling via GPR39 regulates osteoblast function and collagen synthesis, emphasizing its role in maintaining matrix composition. Targeting GPR39 may offer novel therapeutic strategies for osteoporosis and other bone disorders characterized by impaired matrix remodeling.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204776","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}
Martin Oberringer, Martina Jennewein, Monika Bubel, Silke Guthörl, Tim Pohlemann
{"title":"Endothelial Effects in the Elderly: Fibroblast Regulation in Soft Tissue Healing","authors":"Martin Oberringer, Martina Jennewein, Monika Bubel, Silke Guthörl, Tim Pohlemann","doi":"10.1002/jcp.70099","DOIUrl":"https://doi.org/10.1002/jcp.70099","url":null,"abstract":"<p>Two main influencing factors of human soft tissue healing are concomitant diseases and cellular senescence, both accumulating with increasing age. Due to the raising population of the elderly in western countries, it is essential to enhance the level of knowledge concerning the function of senescence in a granulation tissue during repair. The present study was intended to verify classic markers of senescence, like senescence-associated ß-galactosidase and the development of a senescence-associated secretory phenotype among fibroblasts during emerging senescence. The application of an in vitro model using serial passaging as inducer of replicative senescence revealed specific differences of a non-senescent and a pre-senescent fibroblast phenotype in mono-cultures, representing the basis for a detailed examination of the phenotypes in their interaction with microvascular endothelial cells in co-cultures. The results deliver new insights into the age dependent process of tissue repair. Characteristics of pre-senescent fibroblasts in terms of modified proliferation, cell morphology, cell cycle regulation, myofibroblastoid differentiation and cytokine release indicate a strong responsibility of this phenotype for the composition and function of a granulation tissue at different locations, including vascular sites. In its entirety, the results support the assumption, that a missing clearance of the senescence phenotype in late stages of tissue repair is one of the main reasons for healing failure.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204777","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":"Hypoxia Increases Sarcolemmal Na+/HCO3− Cotransport Activity via an ERK1/2-Dependent Pathway in Cardiac HL-1 Cell Line","authors":"Gül Şimşek, Pawel Swietach, Hilmi Burak Kandilci","doi":"10.1002/jcp.70097","DOIUrl":"https://doi.org/10.1002/jcp.70097","url":null,"abstract":"<div>\u0000 \u0000 <p>As a major modulator of cardiac function, intracellular pH (pH<sub>i</sub>) is tightly controlled by sarcolemmal acid–base transporters to within narrow limits (7.1–7.3). Na<sup>+</sup>/H<sup>+</sup> exchanger (NHE1) and Na<sup>+</sup>/HCO<sub>3</sub><sup>−</sup> cotransporter (NBC) are the main acid-extruding membrane proteins; the latter is further subdivided into electrogenic (NBCe1/NBCe2) and electroneutral (NBCn1) isoforms. In the underperfused heart, acid disturbances are often accompanied by hypoxia, but their interplay on cardiac NBC activity is unknown. Here, we studied the effect of acute (1 mM dithionite and 100% N<sub>2</sub>, 10 min) and long-term hypoxia (1% O<sub>2</sub>, 48 h) on sarcolemmal NBC activity using fluorimetric assays in mouse atrial-derived HL-1 cells and primary rat cardiomyocytes. NBCe1 and NBCn1 transcripts were detected in HL-1 cells. Ensemble NBC activity, defined as the HCO<sub>3</sub><sup>−</sup>-dependent acid-extrusion flux, was promptly inhibited under acute anoxia. In contrast, pH<sub>i</sub>-sensitivity of NBC flux was increased after long-term hypoxia, likely an adaptive response. This increase was not due to buffering capacity changes but was mimicked by dimethyloxalylglycine (1 mM, DMOG), which stabilizes hypoxia inducible factor under normoxic conditions. Hypoxia affected neither NBCn1 nor NBCe1 protein levels, indicating a modulatory effect on transporter activity. The contribution of electrogenic (NBCe1) and electroneutral (NBCn1) isoforms, dissected from fluxes generated under hyperkalemia, showed that long-term hypoxia selectively raised NBCn1 activity. This effect was blocked by U0126, an inhibitor of extracellular signal-regulated kinase 1/2, implicating phosphorylation. Our results show that acute anoxia and prolonged hypoxia regulate NBC-dependent flux by distinct mechanisms ostensibly to retain pH control under the combination of acidosis and hypoxia.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glycolysis Plays a Critical and Dual Role in Periodontitis","authors":"Hongyu Ming, Yingyao Li, Tongyun Chen, Xinze Wu, Xudong Xie","doi":"10.1002/jcp.70098","DOIUrl":"10.1002/jcp.70098","url":null,"abstract":"<div>\u0000 \u0000 <p>Glycolysis is a fundamental metabolic pathway that breaks down glucose into pyruvate and lactate, critically shaping immune responses and cell functions in various diseases. Periodontitis is a chronic inflammatory disease marked by progressive destruction of periodontal tissues. Recent evidence has revealed that glycolysis plays a critical and dual role in periodontitis. On one hand, metabolic reprogramming toward glycolysis amplifies inflammatory cascades in various periodontal cells, driving periodontitis progression through multiple mechanisms. On the other hand, the end-product of glycolysis, lactate, and its lactylation exert anti-inflammatory effects in periodontitis by modulating immune responses and regulating bone remodeling. Moreover, emerging therapeutic strategies targeting glycolytic flux aim to inhibit periodontal inflammation progression and promote periodontal tissue regeneration. In this review, we illustrate the dual mechanisms of glycolysis in periodontitis pathogenesis and highlight its potential as a therapeutic target for metabolic intervention.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saroj Gourkanti, Yazmin Munoz, Jacqueline Cheung, Rosa M. Chavez, Devanshi Agarwal, Taylor J. Schoen, Kristina Solorio-Kirpichyan, Sonya E. Neal
{"title":"Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease","authors":"Saroj Gourkanti, Yazmin Munoz, Jacqueline Cheung, Rosa M. Chavez, Devanshi Agarwal, Taylor J. Schoen, Kristina Solorio-Kirpichyan, Sonya E. Neal","doi":"10.1002/jcp.70094","DOIUrl":"10.1002/jcp.70094","url":null,"abstract":"<p>The rhomboid superfamily, comprising both proteases and pseudoproteases, has emerged as a central regulator of membrane biology, mediating diverse functions including protein quality control, signal transduction, trafficking, and more. While molecular mechanisms of rhomboid activity have been well-characterized in invertebrate and cell-based systems, their physiological role in vertebrate development remains limited and continues to evolve. Here, we review recent advances in cell culture systems and vertebrate models that uncover the developmental and disease-relevant functions of rhomboid family members, including RHBDLs, iRhoms, PARL, and Derlins. We outline their roles in embryogenesis, tissue regeneration, neurodevelopment, and immune signaling, alongside their pathological involvement in cancer, neurodegeneration, and metabolic disorders. We also emphasize the limitations posed by early embryonic lethality in knockout models and advocate for tissue-specific vertebrate models to dissect rhomboid-dependent pathways in vivo. Understanding how rhomboid proteins coordinate developmental processes will not only reveal fundamental principles of membrane-associated processes, but also open new avenues for therapeutic targeting in disease.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186003","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}
Kristina Gebhardt, Anne Hebecker, Natascha Sommer, Robert Ringseis, Klaus Eder, Magdalena Huber, Hartmann Raifer, Karsten Krüger, Christopher Weyh
{"title":"PBMCs Mitochondrial Respiration and Its Relation to Immunity, Fitness, and Metabolic Risk in the Healthy Elderly","authors":"Kristina Gebhardt, Anne Hebecker, Natascha Sommer, Robert Ringseis, Klaus Eder, Magdalena Huber, Hartmann Raifer, Karsten Krüger, Christopher Weyh","doi":"10.1002/jcp.70096","DOIUrl":"https://doi.org/10.1002/jcp.70096","url":null,"abstract":"<p>Mitochondrial function plays a central role in regulating immunological and metabolic processes, particularly during successful aging. This cross-sectional study aimed to investigate associations between mitochondrial respiration of peripheral blood mononuclear cells (PBMCs; MR<sub>PBMC</sub>) and key markers of immune function, systemic inflammation, and metabolic health in a cohort of healthy older adults. Sixteen healthy, physically active participants aged > 55 years (male: <i>n</i> = 9; female: <i>n</i> = 7; age: 64 ± 3.7 years; BMI: 24.3 ± 2.9; VO<sub>2peak</sub>: 31.1 ± 8.8 mL/min/kg) were recruited. Participants were tested for their maximal oxygen uptake (VO<sub>2peak</sub>) as well as cardiovascular and metabolic risk factors. Venous fasting blood samples were collected. For further analysis, MR<sub>PBMC</sub> was measured using the Oroboros O2k-Oxygraph. T cell subsets were analyzed by flow cytometry, serum cytokines by LUMINEX assays, and gene expression by qPCR analysis. We found positive associations between basal and maximal MR<sub>PBMC,</sub> and the percentage of CD4<sup>+</sup> T cells, with a notable link to naïve CD4<sup>+</sup> T cells (<i>p</i> < 0.05). Maximal MR<sub>PBMC</sub> was negatively associated with proportion of effector memory CD4<sup>+</sup> T cells (<i>p</i> < 0.05). Basal MR<sub>PBMC</sub> showed negative associations with pro-inflammatory serum cytokine tumor necrosis factor alpha (TNF-α), while maximal MR<sub>PBMC</sub> was positively associated with interleukin 8 (IL-8), intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor (VEGF) (<i>p</i> < 0.05). Intracellular signaling markers, including mRNA level of signal transducer and activator of transcription 3 (STAT3), also showed positive associations with maximal MR<sub>PBMC</sub> (<i>p</i> < 0.05). No correlations were found for variables such as cardiorespiratory fitness, IL-6, and IL-10. In conclusion, PBMC mitochondrial bioenergetics are linked to T cell subpopulations and systemic inflammation in healthy older adults. Higher mitochondrial respiration reflecting better mitochondrial function favors a more naïve CD4<sup>+</sup> T cell distribution. In contrast, lower mitochondrial function was observed in individuals with a more pro-inflammatory profile, suggesting a potential relationship between immune status and mitochondrial bioenergetics in older adults.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146991","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":"Mitochondrial Ca2+ in Cancer Growth and Metabolism","authors":"Jillian S. Weissenrieder, J. Kevin Foskett","doi":"10.1002/jcp.70093","DOIUrl":"10.1002/jcp.70093","url":null,"abstract":"<p>Cancer is a leading cause of death in developed countries, despite many breakthroughs in targeted small molecule and immunotherapeutic interventions. A deeper understanding of the characteristics and processes that underlie malignancy will enable us to develop more effective therapeutic options to improve patient outcomes. One particular area of interest is in cancer cell metabolism. Even as early as the 1920s, Otto Warburg recognized dysregulated metabolism in cancerous cells. Altered metabolism may provide targetable nutrient dependencies for further clinical development, either by nutrient restriction or pathway inhibition. More recently, researchers have observed an increasingly strong linkage between altered mitochondrial Ca<sup>2+</sup> homeostasis and tumor cell metabolism, with strong implications for therapeutic targeting. In this review, we summarize the literature surrounding mitochondrial Ca<sup>2+</sup> homeostasis, metabolism, and cancer, as well as providing a discussion of the potential for mitochondrial Ca<sup>2+</sup> modulation as an anticancer therapeutic modality.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124670","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":"Intermediate Conductance Calcium-Dependent Potassium Channel (KCa3.1) Interacting Proteins Using Turboid-Based Proximity Labeling Technology: Insights Into Interactome and Related Signaling Pathways in Pancreatic Tumors","authors":"Veronica Carpanese, Soha Sadeghi, Luca Matteo Todesca, Ildikò Szabò, Vanessa Checchetto","doi":"10.1002/jcp.70092","DOIUrl":"https://doi.org/10.1002/jcp.70092","url":null,"abstract":"<p>K<sub>Ca</sub>3.1 ion channel is a calcium-activated potassium channel expressed in various tissues, showing dual localization to the plasma membrane and to mitochondria. This channel is highly expressed in numerous cancers and has been implicated in the regulation of proliferation and migration. The molecular details of the signaling pathways linked to regulation exerted by K<sub>Ca</sub>3.1 in cancer cells are, however, not fully elucidated yet. Therefore, we determined the interactome of K<sub>Ca</sub>3.1 using proximity labeling in intact KPC pancreatic cancer cells that mirror the aggressive metastatic behavior of human pancreatic cancer. The results highlight several novel interactors, including those residing in intracellular membranes. The K<sub>Ca</sub>3.1 channel proxisome and related pathways are discussed in light of our current knowledge about K<sub>Ca</sub>3.1 and pancreatic cancer, available in public databases.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062497","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}