The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.
LKB1/STK11 suppresses cyclooxygenase-2 induction and cellular invasion through PEA3 in lung cancer.
Sunil Upadhyay; Chunyan Liu; Aditi Chatterjee; Mohammad O Hoque; Myoung Sook Kim; James Engles; William Westra; Barry Trink; Edward Ratovitski; David Sidransky (Profiled Authors: David Sidransky; Edward Ratovitski; Aditi Chatterjee; Mohammad Hoque; Myoung Kim; William Westra; Barry Trink)
Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Cancer research 2006;66(16):7870-9.
We showed that the PEA3 transcriptional factor interacted with LKB1, a serine/threonine kinase, which is somatically mutated in lung cancer. This interaction occurred through the ETS domain of PEA3 and the kinase domain of LKB1. Mutation of LKB1 in lung cancer cells stabilized PEA3. Reintroduction of wild-type (WT) LKB1 into cells induced down-regulation of PEA3 and subsequently resulted in reduced cyclooxygenase-2 RNA and protein expression, whereas germ-line and somatic LKB1 mutants were defective in this activity. LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism. Cells expressing mutant LKB1 possessed greater invasive potential compared with cells expressing WT LKB1. Increased invasion of cells with mutant LKB1 was partly due to PEA3 expression, as RNA interference inhibition of PEA3 resulted in dramatic decrease of Matrigel invasion. However, forced expression of PEA3 resulted in down-regulation of epithelial markers and induction of mesenchymal markers. These results suggest that PEA3 stabilization due to LKB1 inactivation could lead to epithelial/mesenchymal transition and greater lung cancer invasion potential.
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