Functional role of the Ca2+-activated Cl− channel DOG1/TMEM16A in gastrointestinal stromal tumor cells

Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance

“…118,[135][136][137][138] ANO1 is upregulated in several cancer tissues including head and neck squamous cell carcinoma, prostate, breast, pancreatic cancer and gastrointestinal stromal tumor cells. 120,[139][140][141][142] Figure 14A and 14B show overexpression of ANO1 at the mRNA level and the protein level, respectively, in PDAC cells compared to normal human pancreatic ductal epithelium cells (HPDE). Finally, the functional expression of ANO1 was assessed using the whole-cell patch-clamp technique (steady-state I-V relationship) and cells transfected with scrambled siRNA or siRNA targeting ANO1.…”

“…Inhibition of ANO1 is shown to shift gastrointestinal stromal tumor cells from early apoptotic to late apoptotic stages. 140 ANO6 has received more attention in relation to apoptosis compared to ANO1 and in particular its role as a putative scramblase involved in the redistribution of phospholipids between the outer/inner membrane during apoptosis. 118,152,153 siRNA K D of ANO6 reduces cisplatin induced Caspase 3 activation (apoptosis) in ELA cells (Fig.…”

DOG1 is a sensitive and specific immunohistochemical marker for diagnosis of canine gastrointestinal stromal tumors

“…19,47,48 Studies have demonstrated DOG1 activity in GIST cells, with modest effects on cell viability and proliferation in vitro and oncogenic activity in GIST xenografts in vivo. 3,46 Amplification of the genomic location of human DOG1 (chromosome band 11q13) has been noted in other cancers including squamous cell carcinomas of the head and neck (SCCHN) where DOG1 overexpression is associated with both a poor prognosis in patients and gain of metastatic characteristics in SCCHN cells. 1 The canine DOG1 protein is located on chromosome 18 and shares high homology with the human protein.…”

Patent Highlights

“…The transmembrane protein 16a (TMEM16A; anoctamin-1) is encoded on the long arm of chromosome 11 (region 11q13) and is highly overexpressed in several tumors, especially gastrointestinal stromal tumor and head and neck cancers [27]. Before it was shown to be a component of a calcium-activated chloride channel [28,29] it had been known as the cancer marker, DOG1 [30]. The invention provides antibodies and engineered proteins that specifically bind to the extracellular domain 2 or 3 of TMEM16A (minimum binding domains KLIRYLKLKQ and RYKDYREPPWS), and internalize upon binding.…”