Citation
- Authors: Crottes, D., Lin, Y. T., Peters, C. J., Gilchrist, J. M., Wiita, A. P., Jan, Y. N., Jan, L. Y.
- Year: 2019
- Journal: Proc Natl Acad Sci U S A 116 13026-13035
- Applications: in vitro / siRNA / jetPRIME
- Cell type: AsPC-1
Description: Human pancreatic cells
Method
50 nM siRNA in 6-well plate
Abstract
Pancreatic cancer typically spreads rapidly and has poor survival rates. Here, we report that the calcium-activated chloride channel TMEM16A is a biomarker for pancreatic cancer with a poor prognosis. TMEM16A is up-regulated in 75% of cases of pancreatic cancer and high levels of TMEM16A expression are correlated with low patient survival probability. TMEM16A up-regulation is associated with the ligand-dependent EGFR signaling pathway. In vitro, TMEM16A is required for EGF-induced store-operated calcium entry essential for pancreatic cancer cell migration. TMEM16A also has a profound impact on phosphoproteome remodeling upon EGF stimulation. Moreover, molecular actors identified in this TMEM16A-dependent EGFR-induced calcium signaling pathway form a gene set that makes it possible not only to distinguish neuro-endocrine tumors from other forms of pancreatic cancer, but also to subdivide the latter into three clusters with distinct genetic profiles that could reflect their molecular underpinning.