Kunzelmann, Karl and Ousingsawat, Jiraporn and Benedetto, Roberta and Cabrita, Ines and Schreiber, Rainer (2019) Contribution of Anoctamins to Cell Survival and Cell Death. CANCERS, 11 (3): 382. ISSN 2072-6694
Full text not available from this repository. (Request a copy)Abstract
Before anoctamins (TMEM16 proteins) were identified as a family of Ca2+-activated chloride channels and phospholipid scramblases, the founding member anoctamin 1 (ANO1, TMEM16A) was known as DOG1, a marker protein for gastrointestinal stromal tumors (GIST). Meanwhile, ANO1 has been examined in more detail, and the role of ANO1 in cell proliferation and the development of different types of malignomas is now well established. While ANO5, ANO7, and ANO9 may also be relevant for growth of cancers, evidence has been provided for a role of ANO6 (TMEM16F) in regulated cell death. The cellular mechanisms by which anoctamins control cell proliferation and cell death, respectively, are just emerging; however, the pronounced effects of anoctamins on intracellular Ca2+ levels are likely to play a significant role. Recent results suggest that some anoctamins control membrane exocytosis by setting Ca-i(2+) levels near the plasma membrane, and/or by controlling the intracellular Cl- concentration. Exocytosis and increased membrane trafficking induced by ANO1 and ANO6 may enhance membrane expression of other chloride channels, such as CFTR and volume activated chloride channels (VRAC). Notably, ANO6-induced phospholipid scrambling with exposure of phosphatidylserine is pivotal for the sheddase function of disintegrin and metalloproteinase (ADAM). This may support cell death and tumorigenic activity of IL-6 by inducing IL-6 trans-signaling. The reported anticancer effects of the anthelminthic drug niclosamide are probably related to the potent inhibitory effect on ANO1, apart from inducing cell cycle arrest through the Let-7d/CDC34 axis. On the contrary, pronounced activation of ANO6 due to a large increase in intracellular calcium, activation of phospholipase A2 or lipid peroxidation, can lead to ferroptotic death of cancer cells. It therefore appears reasonable to search for both inhibitors and potent activators of TMEM16 in order to interfere with cancer growth and metastasis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CA2+-ACTIVATED CL-CHANNEL; GASTROINTESTINAL STROMAL TUMORS; REGULATED ANION CHANNEL; PLASMA-MEMBRANE PROTEIN; LEUCINE-RICH REPEAT; CHLORIDE CHANNEL; ESSENTIAL COMPONENT; VOLUME REGULATION; PROSTATE-CANCER; DOWN-REGULATION; anoctamin; ANO1; ANO6; TMEM16A; TMEM16F; cancer; proliferation; apoptosis; Ca2+ signaling; inflammation |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Petra Gürster |
| Date Deposited: | 27 Mar 2020 07:49 |
| Last Modified: | 27 Mar 2020 07:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27399 |
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