title: PF-3758309, p21-activated kinase 4 inhibitor, suppresses migration and invasion of A549 human lung cancer cells via regulation of CREB, NF-κB, and β-catenin signalings.
abstract: Migration and invasion comprise key steps in cancer metastasis. Through the migration and invasion into and out of lymphatic and/or blood vessels, cancer cells can be spread out into the tissues in remote site from the origin. Degradation of extracellular matrix (ECM) must be preceded prior to the metastasis of cancer cells. Matrix metalloproteinases (MMP) can degrade ECM, thus allow cells to migrate from the original site. Among MMPs, two gelatinase MMP-2 and MMP-9 play particularly important roles in ECM degradation. Here, we report that recently developed p21-activated kinase 4 inhibitor PF-3758309 shows anti-metastatic effect in A549 human lung cancer cell. PF-3758309 suppresses CREB, NF-κB, and β-catenin pathways, which are well known to be closely related with cell migration. This leads to the downregulation of MMP-2/MMP-9 expressions and the inhibition of A549 lung cancer metastasis.
authors.affiliation: Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Yuseong-Gu, Taejon, 305-600, Korea.
authors.forename: Byung Jun
authors.initials: BJ
authors.lastname: Ryu
authors.forename: Hyuk
authors.initials: H
authors.lastname: Lee
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung-Nyoung
authors.initials: JN
authors.lastname: Heo
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Yeon
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D011720:Pyrazoles / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051176:beta Catenin / Q000235:genetics*; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors*
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; C550923:PF 3758309; D011720:Pyrazoles; D011758:Pyrroles; D051176:beta Catenin; C116367:PAK4 protein, human; D054462:p21-Activated Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9