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

Molecular and Cellular Biochemistry
Byung Jun RyuSang Yeol Lee

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.

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Citations

Jan 28, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Irene Ramos-ÁlvarezRobert T Jensen
Nov 29, 2015·Journal of Clinical Pathology·Kenta KobayashiTatsuyuki Kawano
Jun 9, 2017·BMC Medical Genomics·Salem A El-AaragMahmoud ElHefnawi
Aug 18, 2017·Omics : a Journal of Integrative Biology·Hitendra S SolankiAditi Chatterjee
Jul 7, 2017·Frontiers in Cellular and Infection Microbiology·Wen HeJing Ye

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