Journal article
TRPM8 ion channel is aberrantly expressed and required for preventing replicative senescence in pancreatic adenocarcinoma: Potential role of TRPM8 as a biomarker and target
Cancer biology & therapy, Vol.13(8), pp.592-599
06/01/2012
DOI: 10.4161/cbt.20079
PMCID: PMC3408969
PMID: 22555807
Abstract
Pancreatic adenocarcinoma is mostly fatal and generally resistant to conventional treatments, such that effective therapies with tolerable side effects are desperately needed. Ion channels including the transient receptor potential (TRP) channels have been implicated in human malignancies, but their roles in pancreatic cancer were mostly unknown. Recent identification of the melastatin-subfamily members of the TRP family of ion channels, and their functions in pancreatic epithelia and adenocarcinoma, is expected to provide a new perspective to understanding the mechanism underlying pancreatic tumorigenesis. In this report, we present the clinical and pathological features of a mini-series of patients with pancreatic adenocarcinoma, which aberrantly exhibits immunoreactivity against the TRPM8 channel. We have recently demonstrated the proliferative role of TRPM8 channel in pancreatic cancer cells. Here, we present evidence that RNA interference-mediated silencing of
TRPM8
induces replicative senescence in pancreatic adenocarcinoma cells. This suggests that the aberrantly expressed TRPM8 channel may contribute to pancreatic tumorigenesis by preventing oncogene-induced senescence, and targeted inhibition of TRPM8 may enhance tumor sensitivity to therapeutics. Based on these observations, we hypothesize that the TRPM8 ion channel plays a crucial role in the growth and progression of pancreatic neoplasia during tumorigenesis. We propose that TRPM8 can be exploited as a clinical biomarker and as a therapeutic target for developing personalized therapy in pancreatic adenocarcinoma.
Details
- Title: Subtitle
- TRPM8 ion channel is aberrantly expressed and required for preventing replicative senescence in pancreatic adenocarcinoma: Potential role of TRPM8 as a biomarker and target
- Creators
- Nelson S Yee - Penn State Milton S. Hershey Medical CenterRobert D Brown - Roy J. and Lucille A. Carver College of MedicineMin Sun Lee - Roy J. and Lucille A. Carver College of MedicineWeiqiang Zhou - Roy J. and Lucille A. Carver College of MedicineChris Jensen - University of Iowa Hospitals and ClinicsHenning Gerke - University of Iowa Hospitals and ClinicsRosemary K Yee - Pennsylvania State University
- Resource Type
- Journal article
- Publication Details
- Cancer biology & therapy, Vol.13(8), pp.592-599
- Publisher
- Landes Bioscience
- DOI
- 10.4161/cbt.20079
- PMID
- 22555807
- PMCID
- PMC3408969
- ISSN
- 1538-4047
- eISSN
- 1555-8576
- Language
- English
- Date published
- 06/01/2012
- Academic Unit
- Gastroenterology and Hepatology; Pathology; Internal Medicine
- Record Identifier
- 9984186657202771
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