TMEM16A controls EGF-induced calcium signaling implicated in pancreatic cancer prognosis.
David CrottèsYu-Hsiu T LinChristian J PetersJohn M GilchristArun P WiitaYuh Nung JanLily Yeh JanPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
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.
Keyphrases
- poor prognosis
- signaling pathway
- high glucose
- small cell lung cancer
- cell migration
- diabetic rats
- long non coding rna
- growth factor
- epidermal growth factor receptor
- tyrosine kinase
- genome wide
- pi k akt
- epithelial mesenchymal transition
- transcription factor
- drug induced
- gene expression
- autism spectrum disorder
- endothelial cells
- induced apoptosis
- free survival