Metastasis-associated protein 2 promotes the metastasis of non-small cell lung carcinoma by regulating the ERK/AKT and VEGF signaling pathways

Abstract

Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer-associated mortality in the world and accounts for ~85% of human lung cancers. Metastasis-associated protein 2 (MTA2) is a component of the histone deacetylase complex and serves a role in tumor progression; however, the mechanism through which MTA2 is involved in the progression of NSCLC remains unclear. The aim of the present study was to investigate the expression and function of MTA2 and the MTA2-mediated signaling pathway in NSCLC cells. Expression of MTA2 and its target genes was analyzed in MTA2-overexpressing and anti-MTA2 antibody (AbMTA2)-treated NSCLC cells, as well as growth, migration, invasion and apoptotic-resistance. The inhibitory effects on tumor formation were analyzed using AbMTA2-treated NSCLC cells and in a mouse model. Histological assessment was conducted to analyze the expressions levels of extracellular signal-regulated kinase (ERK), RAC-α serine/threonine protein kinase (AKT) and vascular endothelial growth factor (VEGF) in experimental tumors. Results of the present study demonstrated that MTA2 was overexpressed in NSCLC cells. The growth, migration and invasion of NSCLC cells were markedly inhibited by AbMTA2. In addition, it was observed that the ERK/AKT and VEGF signaling pathways were both upregulated in MTA2-overexpressing NSCLC cells, and downregulated following silencing of MTA2 activation. ERK and AKT phosphorylation levels were downregulated in NSCLC cells and tumors following MTA2 silencing. The in vivo study demonstrated that tumor growth was markedly inhibited following siRNA-MTA2 treatment. In conclusion, the results of the present study suggested that MTA2 silencing may significantly inhibit the growth and aggressiveness of NSCLC cells. Results from the present study indicated that the mechanism underlying the MTA2-mediated invasive potential of NSCLC cells involved the ERK/AKT and VEGF signaling pathways, which may be a potential therapeutic target for the treatment of NSCLC.

Metastasis-associated protein 2 regulates human hepatocellular carcinoma metastasis progression through modulating p38MAPK/MMP2 pathways

“…Downregulation of MTA2 through the suppression of both the PI3K/AKT and MAPK/ERK pathways ultimately leads to the inhibition of breast tumor growth 32. Silencing MTA2 inhibits the invasive potential of NSCLC cells through the ERK/AKT and VEGF signaling pathways 33. In the present study, the inhibitory effect of MTA2 knockdown on the migration and invasion of HCC cells by inactivating the p38MAPK signaling pathway was confirmed.…”

Nickel‐induced VEGF expression via regulation of Akt, ERK1/2, NFκB, and AMPK pathways in H460 cells

“…That vascular endothelial growth factor (VEGF)‐mediated angiogenesis has a vital role in tumor‐associated metastasis is widely accepted . Several studies have reported that VEGF molecules are critical components in the pathogenesis of non‐small‐cell lung cancer (NSCLC) cells . Clinical studies have demonstrated that serum VEGF levels and tumor size (and microvessel density) are significantly correlated in patients with NSCLC .…”

An isoflavone derivative potently inhibits the angiogenesis and progression of triple-negative breast cancer by targeting the MTA2/SerRS/VEGFA pathway

“…The potential target of MEQ, MTA2, as one nonenzymatic subunit in the NuRD complex, confers functional specificity for the NuRD complex by associating with different transcription factors or targeting distinct gene loci 50 . Moreover, MTA2 is found to be overexpressed in human breast cancer 51 , and the VEGF signaling pathway was able to be modulated by targeting MTA2 expression in non small cell lung cancer cells 52 . Thus, characterizing drugs that target NuRD subunits for cancer therapy should be more specific and effective than those targeting pan-epigenetic modification enzymes.…”