Calcium-Activated Chloride Channel ANO1/TMEM16A: Regulation of Expression and Signaling

Dulin, Nickolai O.

doi:10.3389/fphys.2020.590262

Cited by 34 publications

(21 citation statements)

References 96 publications

(144 reference statements)

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“…Although it has been recently reported that TMEM16A activated EGFR signaling pathway in HNSCC, breast cancer and pancreatic cancer (15,30,31,50,51). However, in this study, we did not find that TMEM16A was significantly associated with EGFR in human CRC tissues.…”

Section: Discussioncontrasting

confidence: 92%

“…For example, TMEM16A mRNA expression might be regulated by other factors such as hypermethylation of the TMEM16A promoter, the signal transducer and activator of transcription (STAT) and some soluble factors in the tumor micro-environment at the transcriptional level during lymph node metastasis. TMEM16A expression might be controlled by a number of microRNAs such as miR-9, miR-144, and miR-132 at translational level, as previously reported ( 13 , 26 , 52 ). TMEM16A protein might interact with other molecular targets including ERK1/2, AKT, camodulin kinase II (CaMKII), EGFR, secreted calcium-activated chloride channel regulator 1 (CLCA1), and Coatomer protein complex subunit beta 1 (COPB1) at post-translational level.…”

Section: Discussionsupporting

confidence: 68%

“…Previous studies demonstrated that TMEM16A expression could be regulated at transcriptional, translational, and post-translational level, and TMEM16A expression is able to modulate different molecules through multiple ways in various cancers ( 52 ). Based on our results, we speculated that MSH2 might be involve in regulating of TMEM16A mRNA expression at transcriptional level or act as a regulator in the translation process of TMEM16A, while KRAS and p53 might interact with TMEM16A protein at post-translational level.…”

Section: Discussionmentioning

confidence: 99%

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Expression of TMEM16A in Colorectal Cancer and Its Correlation With Clinical and Pathological Parameters

Yang

Huo

et al. 2021

Front. Oncol.

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TMEM16A is a recently identified calcium-activated chloride channel (CaCC) and its overexpression contributes to tumorigenesis and progression in several human malignancies. However, little is known about expression of TMEM16A and its clinical significance in colorectal cancer (CRC). TMEM16A mRNA expression was determined by quantitative real time-PCR (qRT-PCR) in 67 CRC tissues and 24 para-carcinoma tissues. TMEM16A protein expression was performed by immunohistochemistry in 80 CRC tissues. The correlation between TMEM16A expression and clinicopathological parameters, and known genes and proteins involved in CRC was analyzed. The results showed that TMEM16A mRNA expression was frequently detected in 51 CRC tissues (76%), whereas TMEM16A protein expression was determined at a relatively lower frequency (26%). TMEM16A mRNA expression in tumor tissues was higher than its expression in normal para-carcinoma tissues (P < 0.05). TMEM16A mRNA expression was significantly correlated with TNM stage (p = 0.039) and status of lymph node metastasis (p = 0.047). In addition, there was a strong positive correlation between TMEM16A mRNA expression and MSH2 protein. More importantly, TMEM16A protein expression was positively associated with KRAS mutation, and negatively correlated with mutant p53 protein. Logistic regression analysis demonstrated that TMEM16A mRNA expression was an important independent predictive factor of lymph node metastasis (OR = 16.38, CI: 1.91–140.27, p = 0.01). TMEM16A mRNA and protein expression was not significantly related with patient survival. Our findings provide original evidence demonstrating TMEM16A mRNA expression can be a novel predictive marker of lymph node metastasis and TMEM16A protein expression may be an important regulator of tumor proliferation and metastasis in CRC.

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Section: Discussioncontrasting

confidence: 92%

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Expression of TMEM16A in Colorectal Cancer and Its Correlation With Clinical and Pathological Parameters

Yang

Huo

et al. 2021

Front. Oncol.

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“…Huang et al [58] showed that TMEM16C binds the Na +activated K + channel Slack, increasing the single-channel activity and sodium sensitivity of Slack channels; structural data by Pan et al [59] revealed that TMC1 channels share a common architecture with the TMEM16 channel, raising the possibility that some TMCbinding proteins could also bind TMEM16F; Avalos-Prado et al [60] reported that KCNE1 is an auxiliary subunit of TMEM16A. However, also several other modulators including cholesterol, fatty acids, phosphorylation, have been shown to regulate the activity of some TMEM16 family members [4,61].…”

Section: Ion Selectivitymentioning

confidence: 99%

Anion and Cation Permeability of the Mouse TMEM16F Calcium-Activated Channel

Stabilini

Menini

Pifferi

2021

IJMS

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TMEM16F is involved in several physiological processes, such as blood coagulation, bone development and virus infections. This protein acts both as a Ca2+-dependent phospholipid scramblase and a Ca2+-activated ion channel but several studies have reported conflicting results about the ion selectivity of the TMEM16F-mediated current. Here, we have performed a detailed side-by-side comparison of the ion selectivity of TMEM16F using the whole-cell and inside-out excised patch configurations to directly compare the results. In inside-out configuration, Ca2+-dependent activation was fast and the TMEM16F-mediated current was activated in a few milliseconds, while in whole-cell recordings full activation required several minutes. We determined the relative permeability between Na+ and Cl¯ (PNa/PCl) using the dilution method in both configurations. The TMEM16F-mediated current was highly nonselective, but there were differences depending on the configuration of the recordings. In whole-cell recordings, PNa/PCl was approximately 0.5, indicating a slight preference for Cl¯ permeation. In contrast, in inside-out experiments the TMEM16F channel showed a higher permeability for Na+ with PNa/PCl reaching 3.7. Our results demonstrate that the time dependence of Ca2+ activation and the ion selectivity of TMEM16F depend on the recording configuration.

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“…Основными физиологическими эндогенными факторами, вызывающими увеличение экспрессии TMEM16А, являются интерлейкины, эпидермальный фактор роста (epidermal growth factor (EGF) и ангиотензин II [115]. Бактериальный токсин липополисахарид вызывает увеличение экспрессии TMEM16А при развитии рака лёгкого у человека и в альвеолярных эпителиальных клетках мышей [116,117].…”

Section: молекулярные механизмы и взаимодействие с сигнальными путямиunclassified

Calcium-activated chloride channels: structure, properties, role in physiological and pathological processes

Grigoriev

2021

BIOMED KHIM

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Ca2+-activated chloride channels (CaCC) are a class of intracellular calcium activated chloride channels that mediate numerous physiological functions. In 2008, the molecular structure of CaCC was determined. CaCC are formed by the protein known as anoctamine 1 (ANO1 or TMEM16A). CaCC mediates the secretion of Cl– in secretory epithelia, such as the airways, salivary glands, intestines, renal tubules, and sweat glands. The presence of CaCC has also been recognized in the vascular muscles, smooth muscles of the respiratory tract, which control vascular tone and hypersensitivity of the respiratory tract. TMEM16A is activated in many cancers; it is believed that TMEM16A is involved in carcinogenesis. TMEM16A is also involved in cancer cells proliferation. The role of TMEM16A in the mechanisms of hypertension, asthma, cystic fibrosis, nociception, and dysfunction of the gastrointestinal tract has been determined. In addition to TMEM16A, its isoforms are involved in other physiological and pathophysiological processes. TMEM16B (or ANO2) is involved in the sense of smell, while ANO6 works like scramblase, and its mutation causes a rare bleeding disorder, known as Scott syndrome. ANO5 is associated with muscle and bone diseases. TMEM16A interacts with various cellular signaling pathways including: epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPK), calmodulin (CaM) kinases, transforming growth factor TGF-β. The review summarizes existing information on known natural and synthetic compounds that can block/modulate CaCC currents and their effect on some pathologies in which CaCC is involved.

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Calcium-Activated Chloride Channel ANO1/TMEM16A: Regulation of Expression and Signaling

Cited by 34 publications

References 96 publications

Expression of TMEM16A in Colorectal Cancer and Its Correlation With Clinical and Pathological Parameters

Expression of TMEM16A in Colorectal Cancer and Its Correlation With Clinical and Pathological Parameters

Anion and Cation Permeability of the Mouse TMEM16F Calcium-Activated Channel

Calcium-activated chloride channels: structure, properties, role in physiological and pathological processes

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