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

• Published in: Molecular and cellular biochemistry Vol. 389; no. 1-2; pp. 69 - 77
• Main Authors: Ryu, Byung Jun, Lee, Hyuk, Kim, Seong-Ho, Heo, Jung-Nyoung, Choi, Sik-Won, Yeon, Jeong-Tae, Lee, Jeongmin, Lee, Jongsung, Cho, Jae Youl, Kim, Seong Hwan, Lee, Sang Yeol
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.04.2014; Springer
• Subjects: beta Catenin - genetics; Biochemistry; Biomedical and Life Sciences; Cancer; Cancer cells; Cardiology; Cell Line, Tumor; Cell Movement - drug effects; Cell Movement - genetics; Cyclic AMP Response Element-Binding Protein - genetics; Down-Regulation - drug effects; Down-Regulation - genetics; Extracellular Matrix - genetics; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Humans; Life Sciences; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 9 - genetics; Medical Biochemistry; Neoplasm Invasiveness - genetics; NF-kappa B - genetics; Oncology; p21-Activated Kinases - antagonists & inhibitors; Prevention; Pyrazoles - pharmacology; Pyrroles - pharmacology; Signal Transduction - drug effects; Signal Transduction - genetics; NF-κB; PF-3758309; CREB; Matrix metalloproteinases; p21-activated kinase 4; β-Catenin; Metastasis; Human lung cancer
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-013-1928-8

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.