Table 2 Short description of the ECM genes that form a regulatory network
Aspn | (Asporin) is an extracellular matrix protein that modulates the Transforming Growth Factor β (TGFβ) signaling pathway, regulating cartilage matrix gene expression and cartilage formation [60]. Aspn inhibits TGFβ1, a biomarker of poor prognosis in cancer [61]. High asporin expression is significantly associated with less aggressive tumors, which could explain the benign growth. |
Chad | (Chondroadherin) expression has been linked to significant decreases in hepatocellular carcinoma, both in mRNA and protein levels. Chad abundance correlates with differentiation and metastasis, while the reduction of Chad levels significantly enhances proliferation and migration [39]. Chad has a α2β1 integrin binding sequence that previous studies have found counter cancer development [62]. |
Fbln5 | (Fibulin-5) is frequently silenced in lung cancer and suppresses cell invasion by inhibiting the Wnt/β-catenin pathway [63]. Fbln5 has also been shown to reduce reactive oxygen species (ROS) production by modulating cell-ECM interactions [64]. Excessive ROS production results in cellular toxicity, which can promote tumor growth. |
Lum | (Lumican) has different effects on cancer development, depending on the type of tumor and whether Lum is expressed in the cell or in the adjacent stromal tissue [65]. Lum also acts as an oncogene, but if present in the surrounding stroma, it can restrict cancer progression and migration. |
Sfrp1 | (Secreted frizzled-related protein 1) is an antagonist of Wnt signaling, which gives Sfrp1 its tumor-suppressive effect. The loss of Sfrp1 has been hypothesized to activate MAPK or the non-canonical Wnt pathway [66]. One mechanism of how this loss can occur is the methylation of Lum via HP1α. |
Kera | (Keratocan) encodes a protein that is involved in corneal transparency. Mutations can cause cornea plana [67]. |
Omd | (Osteomodulin) is an extracellular matrix keratan sulfate proteoglycan that is also connected to bone development [68]. |
Igf2 | (Insulin-like growth factor 2) is a mitogenic peptide hormone expressed by liver and many other tissues. It is closely associated with cancer [69, 70]. |
Cebpa | (Transcription factor CCAAT / enhancer-binding protein alpha) is an important protein during embryogenesis, glucose metabolism, adipogenesis, and myeloid development [16, 30, 71]. |
Jun | Jun is part of the transcription factor activator protein 1 and has been closely associated with cancer development [15, 72, 73]. |