TMEM16A Controls EGF-induced Calcium Signaling Implicated in Pancreatic Cancer Prognosis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2019 Jun 12

PMID 31182586

Citations 37

Authors

David Crottes

Yu-Hsiu T Lin

Christian J Peters

John M Gilchrist

Arun P Wiita

Yuh Nung Jan

Lily Yeh Jan

Affiliations

Soon will be listed here.

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.

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