Cell-specific mechanisms of TMEM16A Ca2+-activated chloride channel in cancer

被引:0
作者
Hui Wang
Liang Zou
Ke Ma
Jiankun Yu
Huizhe Wu
Minjie Wei
Qinghuan Xiao
机构
[1] China Medical University,Department of Ion Channel Pharmacology, School of Pharmacy
[2] National Cancer Center/Cancer Hospital,Department of Anesthesiology
[3] Chinese Academy of Medical Sciences and Peking Union Medical College,Department of Pharmacology
[4] School of Pharmacy,undefined
[5] China Medical University,undefined
来源
Molecular Cancer | / 16卷
关键词
TMEM16A; Anoctamin 1; Ca; -activated chloride channel; Tumorigenesis; Signaling; Biomarker;
D O I
暂无
中图分类号
学科分类号
摘要
TMEM16A (known as anoctamin 1) Ca2+-activated chloride channel is overexpressed in many tumors. TMEM16A overexpression can be caused by gene amplification in many tumors harboring 11q13 amplification. TMEM16A expression is also controlled in many cancer cells via transcriptional regulation, epigenetic regulation and microRNAs. In addition, TMEM16A activates different signaling pathways in different cancers, e.g. the EGFR and CAMKII signaling in breast cancer, the p38 and ERK1/2 signaling in hepatoma, the Ras-Raf-MEK-ERK1/2 signaling in head and neck squamous cell carcinoma and bladder cancer, and the NFκB signaling in glioma. Furthermore, TMEM16A overexpression has been reported to promote, inhibit, or produce no effects on cell proliferation and migration in different cancer cells. Since TMEM16A exerts different roles in different cancer cells via activation of distinct signaling pathways, we try to develop the idea that TMEM16A regulates cancer cell proliferation and migration in a cell-dependent mechanism. The cell-specific role of TMEM16A may depend on the cellular environment that is predetermined by TMEM16A overexpression mechanisms specific for a particular cancer type. TMEM16A may exert its cell-specific role via its associated protein networks, phosphorylation by different kinases, and involvement of different signaling pathways. In addition, we discuss the role of TMEM16A channel activity in cancer, and its clinical use as a prognostic and predictive marker in different cancers. This review highlights the cell-type specific mechanisms of TMEM16A in cancer, and envisions the promising use of TMEM16A inhibitors as a potential treatment for TMEM16A-overexpressing cancers.
引用
收藏
相关论文
共 46 条
  • [21] Anion permeation in calcium-activated chloride channels formed by TMEM16A from Xenopus tropicalis
    Reyes, J. P.
    Lopez-Rodriguez, A.
    Espino-Saldana, A. E.
    Huanosta-Gutierrez, A.
    Miledi, R.
    Martinez-Torres, A.
    PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2014, 466 (09): : 1769 - 1777
  • [22] The multiple expression of Ca2+-activated Cl- channels via homo- and hetero-dimer formation of TMEM16A splicing variants in murine portal vein
    Ohshiro, Junya
    Yamamura, Hisao
    Saeki, Takanori
    Suzuki, Yoshiaki
    Imaizumi, Yuji
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2014, 443 (02) : 518 - 523
  • [23] TMEM16A Protein: A New Identity for Ca2+-Dependent Cl- Channels
    Ferrera, Loretta
    Caputo, Antonella
    Galietta, Luis J. V.
    PHYSIOLOGY, 2010, 25 (06) : 357 - 363
  • [24] TMEM16A drives renal cyst growth by augmenting Ca2+ signaling in M1 cells
    Ines Cabrita
    Björn Buchholz
    Rainer Schreiber
    Karl Kunzelmann
    Journal of Molecular Medicine, 2020, 98 : 659 - 671
  • [25] Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1
    Piechowicz, Katarzyna A.
    Truong, Eric C.
    Javed, Kashif M.
    Chaney, Rachelle R.
    Wu, Johnny Y.
    Phuan, Puay W.
    Verkman, Alan S.
    Anderson, Marc O.
    JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2016, 31 (06) : 1362 - 1368
  • [26] Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension
    Forrest, Abigail S.
    Joyce, Talia C.
    Huebner, Marissa L.
    Ayon, Ramon J.
    Wiwchar, Michael
    Joyce, John
    Freitas, Natalie
    Davis, Alison J.
    Ye, Linda
    Duan, Dayue D.
    Singer, Cherie A.
    Valencik, Maria L.
    Greenwood, Iain A.
    Leblanc, Normand
    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2012, 303 (12): : C1229 - C1243
  • [27] Preassociated apocalmodulin mediates Ca2+-dependent sensitization of activation and inactivation of TMEM16A/16B Ca2+-gated Cl- channels
    Yang, Tingting
    Hendrickson, Wayne A.
    Colecraft, Henry M.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (51) : 18213 - 18218
  • [28] Dynamic modulation of ANO1/TMEM16A HCO3- permeability by Ca2+/calmodulin
    Jung, Jinsei
    Nam, Joo Hyun
    Park, Hyun Woo
    Oh, Uhtaek
    Yoon, Joo-Heon
    Lee, Min Goo
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (01) : 360 - 365
  • [29] ER-localized bestrophin 1 activates Ca2+-dependent ion channels TMEM16A and SK4 possibly by acting as a counterion channel
    René Barro-Soria
    Fadi Aldehni
    Joana Almaça
    Ralph Witzgall
    Rainer Schreiber
    Karl Kunzelmann
    Pflügers Archiv - European Journal of Physiology, 2010, 459 : 485 - 497
  • [30] KCNE1 does not shift TMEM16A from a Ca2+ dependent to a voltage dependent Cl- channel and is not expressed in renal proximal tubule
    Khaoula Talbi
    Jiraporn Ousingsawat
    Raquel Centeio
    Rainer Schreiber
    Karl Kunzelmann
    Pflügers Archiv - European Journal of Physiology, 2023, 475 : 995 - 1007