Taken together, the TGFα-EGFR-Akt signaling axis can play a role in enhancing proinflammatory chemokine expression in TNBC, subsequently contributing to the inflammatory burden that ultimately lead to cancer progression and a higher mortality rate among TNBC patients.
The over-expression of epidermal growth factor receptor (EGFR) and its ligands, epidermal growth factor (EGF) and transforming growth factor-alpha, is a common feature of epithelial carcinomas and correlates with neoplastic progression.
It has been demonstrated that vascular endothelial growth factor (VEGF) is associated with tumor progression as an angiogenic factor in esophageal squamous cell carcinoma (SCC)s. However, the role of other angiogenic factors such as transforming growth factor-alpha (TGF-alpha), platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF) are still unknown in esophageal SCCs.
Altogether, these results suggest that the down-regulation of cadherin-11 is a frequent molecular event in the neoplastic transformation of astrocytes and that this down-regulation may be initiated and/or amplified by TGF-alpha autocrine/paracrine loops during tumor progression.
Epidermal growth factor receptor (EGFR), a mediator of mitogenic activity of epidermal growth factor and transforming growth factor-alpha, has been shown to be associated with tumour progression.
Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predicttumor progression.
A trend toward increased expression of EGF-R and TGFalpha protein with dedifferentiation and a similar trend in the growth fraction suggest a role in tumor progression.
It has been believed to play a role in tumor initiation by inducing the reversible transformed phenotype; overexpression of TGF-alpha may be important for tumor progression via autocrine stimulation and oncogene overexpression.
These results indicate that EGF and TGF-alpha successively evoke cascade phenomena which favor tumor progression, invasion and extracellular matrix formation, acting as autocrine growth regulators for gastric carcinomas.
Moreover, they stimulate the expression of metalloproteinase genes suggesting that EGF and TGF-alpha successively evoke cascade phenomena which are most convenient for tumor progression, invasion and metastasis.