Original Article
FAM46B suppresses proliferation, migration and invasion of non-small cell lung cancer via β-catenin/MMP7 signaling
Abstract
Background: This study investigated the functions of FAM46B in non-small cell lung cancer (NSCLC) cells and determined the role of β-catenin/matrix metalloproteinase 7 (MMP7) signaling in mediating these functions.
Methods: Human paracancerous and cancer tissues were collected from lung cancer patients. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay while migration and invasion were examined by transwell chamber assays. Relative mRNA expression and protein levels were determined by quantitative reverse transcription (q-RT) polymerase chain reaction (PCR) and western blot, respectively.
Results: FAM46B displayed reduced expression in lung cancer tissues compared with paired paracancerous tissues. In contrast, β-catenin protein levels were elevated in lung cancer tissues compared with paired paracancerous tissues. FAM46B over-expression reduced proliferation, migration and invasion of A549 and H292 cells, as well as decreased the protein levels of β-catenin, MMP7 and vascular endothelial growth factor (VEGF). On the other hand, FAM46B knockdown by shRNA in H1975 cells enhanced proliferation, migration and invasion, as well as increased the protein levels of β-catenin and MMP7. These enhanced effects were ameliorated by treatment with the Wnt/β-catenin inhibitor XAV939, suggesting a role for Wnt signaling in mediating the functions of FAM46B in NSCLC.
Conclusions: FAM46B functions as a tumor suppressor by inhibiting β-catenin/MMP7 signaling.
Methods: Human paracancerous and cancer tissues were collected from lung cancer patients. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay while migration and invasion were examined by transwell chamber assays. Relative mRNA expression and protein levels were determined by quantitative reverse transcription (q-RT) polymerase chain reaction (PCR) and western blot, respectively.
Results: FAM46B displayed reduced expression in lung cancer tissues compared with paired paracancerous tissues. In contrast, β-catenin protein levels were elevated in lung cancer tissues compared with paired paracancerous tissues. FAM46B over-expression reduced proliferation, migration and invasion of A549 and H292 cells, as well as decreased the protein levels of β-catenin, MMP7 and vascular endothelial growth factor (VEGF). On the other hand, FAM46B knockdown by shRNA in H1975 cells enhanced proliferation, migration and invasion, as well as increased the protein levels of β-catenin and MMP7. These enhanced effects were ameliorated by treatment with the Wnt/β-catenin inhibitor XAV939, suggesting a role for Wnt signaling in mediating the functions of FAM46B in NSCLC.
Conclusions: FAM46B functions as a tumor suppressor by inhibiting β-catenin/MMP7 signaling.
