Combating Lung Cancer Metastasis by Raising Intracellular cAMP Concentration
Abstract
ERK signaling pathway plays a critical role in the survival and proliferation of invasive lung cancer cells. However, mechanism associated the regulation of high ERK activity in invasive lung cancer cells is not defined. This proposal is to test whether ERK activity is regulated by cellular cAMP concentration and particular cyclic nucleotide phosphodiesterase (PDE) isotype. In this study, we show that ERK activity is suppressed by raising cellular cAMP concentration in invasive lung cancers. qRT-PCR reveal that levels of PDE7B and PDE10A mRNA are elevated in invasive lung cancer cell lines in comparison with non-invasive lung cancer cell lines. However, only knockdown of PDE10A reduced ERK activity in invasive lung cancer cells. Moreover, we show that specific PDE10A inhibitor induced significant apoptosis in invasive lung cancer cells. Our study can thus provide a proof-of-concept of potentially using PDE inhibitor to treat metastatic lung cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2013
- Accession Number
- ADA599083
Entities
People
- Shuang Huang
Organizations
- Augusta University