Pan-Cancer Analysis of ANO6 and Experimental Validation in Metastatic Melanoma.

PubMed, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

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Anoctamin 9 determines Ca2+ signals during activation of T-lymphocytes

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Background Activation of T-cells is initiated by an increase in intracellular Ca 2+ , which underlies positive and negative regulation. Because the phospholipid scramblase ion channel ANO9 (TMEM16J) was shown previously to regulated signals renal epithelial cells, we asked whether demonstrates a similar regulation T-cells. Methods We used measurements concentration examine effects on signaling demonstrated expression its cellular molecular parameters. Results found be expressed human lymphocytes, including Jurkat T-lymphocyte cell line mouse lymphocytes. has been affect cells. Here demonstrate essential role during initiation isolated for initial rise due influx extracellular through store-operated ORAI1 entry channels. indispensable T-cell function, independent cells are activated stimulation receptor with CD3-antibody or PMA/phytohemagglutinin. Conclusions Upon activation formation immunological synapse, recruits -ATPase (PMCA) plasma membrane, supported scaffolding protein discs large 1 (DLG1). PMCAs maintain low levels near channels thereby suppressing -inhibition thus retaining (SOCE). It suggested that interorganelle communication trafficking, probably requires function.

Language: Английский

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TMEM16A Maintains Acrosomal Integrity Through ERK1/2, RhoA, and Actin Cytoskeleton During Capacitation

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3750 - 3750

Published: April 16, 2025

Mammalian spermatozoa undergo a series of physiological and biochemical changes in the oviduct that lead them to acquire ability fertilize eggs. During their transit oviduct, face environmental can affect sperm viability. A ion channels transporters, as well cytoskeleton, allow remain viable functional. Cl− such TMEM16A (calcium-activated chloride channel), CFTR (cystic fibrosis transmembrane conductance regulator), ClC3 (chloride voltage-gated channel 3) are some transporters involved maintaining cellular homeostasis. They expressed mammalian associated with capacitation, acrosomal reaction, motility. However, little is known about role volume. Therefore, this study aimed determine mechanism through which maintains volume during capacitation. The effects were compared those ClC3. Spermatozoa capacitated presence specific TMEM16A, CFTR, inhibitors, results showed only inhibition increased volume, leading within acrosome. Similarly, prevented actin polymerization Further analysis also ERK1/2 RhoA activation. On other hand, affected both capacitation spontaneous whereas reaction. In conclusion, activity regulates structure by regulating activities.

Language: Английский

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ANO1: central role and clinical significance in non-neoplastic and neoplastic diseases

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 28, 2025

Anoctamin 1 (ANO1), also known as TMEM16A, is a multifunctional protein that serves calcium-activated chloride channel (CaCC). It ubiquitously expressed across various tissues, including epithelial cells, smooth muscle and neurons, where it integral to physiological processes such secretion, contraction, neural conduction, cell proliferation migration. Dysregulation of ANO1 has been linked the pathogenesis numerous diseases. Extensive research established its involvement in non-neoplastic conditions asthma, hypertension, gastrointestinal (GI) dysfunction. Moreover, garnered significant attention for role development progression cancers, head neck cancer, breast lung overexpression correlates with increased tumor growth, metastasis, poor prognosis. Additionally, regulates multiple signaling pathways, epidermal growth factor receptor (EGFR) pathway, mitogen-activated kinase (MAPK)/extracellular signal-regulated (ERK) phosphatidylinositol 3-kinase (PI3K)/protein B (AKT) among others. These pathways are pivotal regulating proliferation, migration, invasion. Given central these processes, emerged promising diagnostic biomarker therapeutic target. Recent advancements have highlighted potential disease diagnosis treatment. Strategies targeting ANO1, small molecule modulators or gene-silencing techniques, shown preclinical promise both neoplastic This review explores latest findings research, focusing on mechanistic progression, regulation, potential. Modulating activity may offer novel strategies effectively treating ANO1-associated

Language: Английский

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Functional Interdependence of Anoctamins May Influence Conclusions from Overexpression Studies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9998 - 9998

Published: Sept. 17, 2024

Anoctamin 6 (ANO6, TMEM16F) is a phospholipid (PL) scramblase that moves PLs between both plasma membrane (PM) leaflets and operates as an ion channel. It plays role in development essential for hemostasis, bone mineralization immune defense. However, ANO6 has also been shown to regulate cellular Ca2+ signaling PM compartments, thereby controlling the expression of channels such CFTR. Given these pleiotropic effects, we investigated functional interdependence ubiquitous with other commonly co-expressed anoctamins. As most studies on anoctamins use HEK293 human embryonic kidney cells, compared currents, PL scrambling signals induced by overexpression wild-type parental ANO6-knockout cells. The data suggest endogenous significantly affects results obtained from overexpressed anoctamins, particularly after increasing intracellular Ca2+. Thus, significant may influence interpretation analysis

Language: Английский

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