Overexpressed MAGP1 Is Associated With a Poor Prognosis and Promotes Cell Migration and Invasion in Gastric Cancer

Abstract

Gastric cancer (GC) is a frequently occurring malignancy with high mortality rates. However, the underlying mechanism of GC progression is not very clear. The aim of this study is to reveal the inherent molecular mechanism and develop potential therapeutic targets for advanced GC. The microfibril-associated glycoprotein 1 (MAGP1), identified as a potential oncogene, was found upregulated in GC tissues and high MAGP1 expression was associated with aggressive clinicopathological features. Furthermore, the multivariate Cox regression analysis showed that high MAGP1 expression was an independent predictor of poor prognosis (HR = 2.37, 1.07-5.24; P = 0.033). Mechanistically, MAGP1 promoted the migration and invasiveness of GC cells. In addition, the genes co-expressed with MAGP1 were primarily enriched in focal adhesion and PI3K-Akt pathways. MAGP1 overexpression enhanced the phosphorylation of FAK, AKT, and mTOR, whereas its knockdown also inactivated these factors. Furthermore, the AKT inhibitor suppressed the phosphorylation of AKT, FAK, and mTOR in recMAGP1-treated AGS cells, as well as their migration and invasion capacities. Finally, correlation analysis indicated that MAGP1 is involved in AKT signaling in GC, and is clinically relevant. Taken together, MAGP1 is a promising prognostic marker and potential therapeutic target for advanced GC.

Genetically predicted circulating protein biomarkers and ovarian cancer risk

“…DLK1, a noncanonical Notch ligand, has a demonstrated role in promoting ovarian carcinogenesis via Notch activation and epithelial-mesenchymal transition [24]. The microfibrillar-associated protein 2 (MFAP2), previously named microfibril-associated glycoprotein 1 (MAGP1), activates integrin signaling and is a potential oncogene [25][26][27]. Another protein identified at FDR < 0.05, Netrin-G1 or NTNG1, is involved in apoptosis and known to be dysregulated particularly in endocrine-related tumors [28,29].…”

Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

“…MAGP-1 shows a significant role in AT, protecting against obesity and metabolic dysfunction through the regulation of TGF-β in animal models [22]. In addition, a significant involvement of MAGP-1 in tumour progression has also been demonstrated [25,26,[30][31][32]. However, the possible role of MAGP-1 in the remodelling of the AT as a mechanism linking obesity and CC remains unclear.…”

“…Different studies have also implicated MAGP-1 in tumour progression. In this line, MAGP-1 levels are known to be overexpressed in gastric cancer [25] and multiple myeloma [26]. The downregulation of MAGP-1 has been shown to inhibit the migration and invasion of gastric cancer cells with no impact on their capacity of proliferation [25].…”

“…In this line, MAGP-1 levels are known to be overexpressed in gastric cancer [25] and multiple myeloma [26]. The downregulation of MAGP-1 has been shown to inhibit the migration and invasion of gastric cancer cells with no impact on their capacity of proliferation [25]. Interestingly, MAGP-1 has been also implicated in the epithelial-mesenchymal transition (EMT) due to its interaction with TGF-β, SMAD2/3 and WNT/NOTCH pathways [27,28].…”

DUOX2 As a Potential Prognostic Marker which Promotes Cell Motility and Proliferation in Pancreatic Cancer

“…TNM stage, which is the major determinant of appropriate treatment and prognosis, records the primary and regional nodal extent of the tumor and the absence or presence of metastases [ 27 ]. Public data revealed that high DUOX2 expression was positively correlated with early TNM stage, while our clinical study analysis showed that it was positively associated with advanced TNM stage.…”