ANO9 Membrane Protein Introduction

Introduction of ANO9

ANO9 is known as Anoctamin 9, transmembrane member 16J (TMEM16J). It belongs to the transmembrane member 16 (TMEM16) family of proteins, also known as anoctamins (ANOs), mediate diverse physiological functions such as ion transport, phospholipid movement across the membrane, and regulation of other membrane proteins. The structure of ANO9 has not identified so far, however, the predicted topology model of ANO9 extracted from the crystal structure of nhTMEM16 indicates that ANO9 possesses eight transmembrane domains.

Function of ANO9 Membrane Protein

ANO9 is expressed in the human nasal and colonic epithelium, the respiratory, digestive, skeletal and integumentary systems during development, which suggests that ANO9 is involved in a number of physiological processes. Even though ANO9 is also implicated in the metastasis of colorectal cancer, the detailed function and activation mechanism of ANO9 in colorectal tumorigenesis is not known. Besides, the ANO9 mRNA and protein levels are increased in pancreatic cancer-derived cells. It has been reported that exogenous expression of ANO9 in PANC-1 cells can increase cell proliferation in cell cultures and in mice significantly. The knockdown of ANO9 can augment the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation, which suggests the physical association of ANO9 with EGFR. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer. These results show that ANO9 promotes tumorigenesis via EGFR and is a novel therapeutic target for pancreatic cancer.

Fig.1 The predicted and revised model of ANO9 membrane protein (Kim, 2018)

Application of ANO9 Membrane Protein in Literature

1. Kim H., et al. Anoctamin 9/TMEM16J is a cation channel activated by cAMP/PKA signal. Cell Calcium. 2018, 71:75-85. PubMed ID: 29604966
   
   

   This article demonstrates that the native ANO9 in colorectal cells is activated by intracellular cAMP. Meanwhile, the fact that ANO9 transcripts were predominant in the intestines suggests that ANO9 could play a role in intestine function.

2. Jun I., et al. ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer. Br. J. Cancer. 2017, 117:1798. PubMed ID: 29024940
   
   

   This article reveals that ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target because the ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells.

3. Gupta A., et al. Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants. PLOS ONE. 2016, 11(2):e0148649. PubMed ID: 26872154
   
   

   The authors in this article demonstrate that genetic variants within the PKP3-SIGIRR-TMEM16J gene region (PKP3-rs10902158-A/G and TMEM16J- rs7111432 G/A) are significantly associated with a 40% to 70% increased risk for pediatric TB and death.

4. Horne D.J., et al. Common Polymorphisms in the PKP3-SIGIRR-TMEM16J Gene Region Are Associated With Susceptibility to Tuberculosis. The Journal of Infectious Diseases. 2012, 205(4):586-594. PubMed ID: 22223854
   
   

   The results of this article demonstrate a strong association of single nucleotide polymorphisms in the PKP3-SIGIRR-TMEM16J gene region and tuberculosis in discovery and validation cohorts for the first time.

5. Li C., et al. Identification and characterization of ANO9 in stage II and III colorectal carcinoma. Oncotarget. 2015, 6(30):29324-29334. PubMed ID: 26317553
   
   

   This article focuses on the role of ANO9 in progression and metastasis of stage II and III colorectal cancer. The findings in this article suggest that ANO9 could be a novel approach for inhibiting colorectal cancer progression because ANO9 is up-regulated in colorectal cancer patients.

ANO9 Preparation Options

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Reference

1. Kim H., et al. (2018). Anoctamin 9/TMEM16J is a cation channel activated by cAMP/PKA signal. Cell Calcium. 71:75-85.

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