Cancer draws attention owing to the high morbidity and mortality. It is urgent to develop safe and effective cancer therapeutics. The calcium-activated chloride channel TMEM16A is widely distributed in various tissues and regulates physiological functions. TMEM16A is abnormally expressed in several cancers and associate with tumorigenesis, metastasis, and prognosis. Knockdown or inhibition of TMEM16A in cancer cells significantly inhibits cancer development. Therefore, TMEM16A is considered as a biomarker and therapeutic target for some cancers. This work reviews the cancers associated with TMEM16A. Then, the molecular mechanism of TMEM16A overexpression in cancer was analyzed, and the possible signal transduction mechanism of TMEM16A regulating cancer development was summarized. Finally, TMEM16A inhibitors with anticancer effect and their anticancer mechanism were concluded. We hope to provide new ideas for pharmacological studies on TMEM16A in cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.lfs.2023.122034 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modeling ocular surface ion and water transport by generation of lipid- and mucin-producing human Meibomian gland and conjunctival epithelial cells.
Am J Physiol Cell Physiol
January 2025
Laboratoire de Physiopathologie et Régulation des Transports Ioniques, Université de Poitiers, France.
Despite the importance of ocular surface in human physiology and diseases, little is known about ion channel expression, properties and regulation in ocular epithelial cells. Furthermore, human primary epithelial cells have rarely been studied in favor of rat, mouse and especially rabbit animal models. Here, we developed primary human Meibomian gland (hMGEC) and conjunctival (hConEC) epithelial cells.
View Article and Find Full Text PDFPharmacological profiling of small molecule modulators of the TMEM16A channel and their implications for the control of artery and capillary function.
Br J Pharmacol
January 2025
Department of Pharmacology, University of Oxford, Oxford, UK.
Background And Purpose: TMEM16A chloride channels constitute a depolarising mechanism in arterial smooth muscle cells (SMCs) and contractile cerebral pericytes. TMEM16A pharmacology is incompletely defined. We elucidated the mode of action and selectivity of a recently identified positive allosteric modulator of TMEM16A (PAM_16A) and of a range of TMEM16A inhibitors.
View Article and Find Full Text PDFHigh Ano1 expression as key driver of resistance to radiation and cisplatin in HPV-negative head and neck squamous cell carcinoma.
Sci Rep
January 2025
Department of Radiooncology and Radiotherapy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Human papilloma virus-negative head and neck squamous cell carcinoma (HNSCC) frequently harbors 11q13 amplifications. Among the oncogenes at this locus, CCND1 and ANO1 are linked to poor prognosis; however, their individual roles in treatment resistance remain unclear. The impact of Cyclin D1 and Ano1 overexpression on survival was analyzed using the TCGA HNSCC dataset and a Charité cohort treated with cisplatin (CDDP)-based radiochemotherapy.
View Article and Find Full Text PDFThe CLCA1/TMEM16A/Cl- current axis associates with H2S deficiency in diabetic kidney injury.
JCI Insight
January 2025
Center for Precision Medicine, Department of Medicine, and.
The role played by anionic channels in diabetic kidney disease (DKD) is not known. Chloride channel accessory 1 (CLCA1) facilitates the activity of TMEM16A (Anoctamin-1), a Ca2+-dependent Cl- channel. We examined if CLCA1/TMEM16A had a role in DKD.
View Article and Find Full Text PDFTamsulosin ameliorates bone loss by inhibiting the release of Cl through wedging into an allosteric site of TMEM16A.
Proc Natl Acad Sci U S A
January 2025
National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing 100094, China.
TMEM16A, a key calcium-activated chloride channel, is crucial for many physiological and pathological processes such as cancer, hypertension, and osteoporosis, etc. However, the regulatory mechanism of TMEM16A is poorly understood, limiting the discovery of effective modulators. Here, we unveil an allosteric gating mechanism by presenting a high-resolution cryo-EM structure of TMEM16A in complex with a channel inhibitor that we identified, Tamsulosin, which is resolved at 2.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!